Medical fluid injection apparatus and method with detachable patch and monitoring

ABSTRACT

Provided herein are systems and methods for monitoring one or more health or physiological parameters in a subject. The systems and methods may comprise a patch coupled to an injector. Data may be transmitted to a mobile device or remote server, where the data may be processed. Processed data may be used to inform a subject on a health or physiological condition.

CROSS-REFERENCE

This application is a continuation of U.S. patent application Ser. No.17/387,047, filed Jul. 28, 2021, which is a continuation of U.S. patentapplication Ser. No. 16/785,408, filed Feb. 7, 2020, now U.S. Pat. No.11,109,800, which is a continuation of International Patent ApplicationNo. PCT/US2019/069142, filed on Dec. 31, 2019, which claims priority toU.S. Provisional Patent Application No. 62/848,511, filed May 15, 2019,and U.S. Provisional Patent Application No. 62/788,589, filed Jan. 4,2019, each of which is entirely incorporated herein by reference.

BACKGROUND

Vials are one of the preferred reservoirs or container closure systemsused by the pharmaceutical industry due to their extensive clinicalhistory and record of long-term stability with a wide variety of drugs.Pharmaceutical drugs including biologics are provided in standardcontainers such as vials. Additionally, the industry has made asignificant investment in capital equipment for aseptic vial filling.However, vials require the transfer of the contained drug from the vialto an injection device (e.g., injector, autoinjector, infuser, etc.) fordelivery to the patient. New container closure systems such as prefilledsyringes and cartridges have been introduced that allow direct transferof the drug from the syringe or cartridge to the patient. Injectiondevices such as auto-injectors and pens have been developed to utilizethese newer forms of container closure. Because of uncertainty aboutlong-term drug stability, and the extensive manufacturing resourcesalready in place, devices that incorporate standard container closuresystems such as vials, prefilled syringes or cartridges are greatlypreferred by the pharmaceutical industry over devices that require acustom form of drug containment.

However, vials, prefilled syringes and cartridges are not necessarilythe optimum containers for a drug delivery device. This is especiallytrue in the case of delivery devices that deliver relatively highvolumes of drugs (2-50 cc) or high viscosity (over 15 cP and up to about100 cP). Vials, prefilled syringes, and cartridges are almostexclusively cylinders made of glass, which imposes design constraints onforces and geometries. Typical syringes and auto-injectors are limitedon the viscosities of drug that can be delivered as well as by theforces that can be applied to the glass container closure systems. Newinjection devices have been developed including pumps for the deliveryof insulin that use custom container closures, but these systems arevery expensive, cannot generate high forces or pressures and typicallyreusable and/or refillable.

On-body injection devices have been the subject of continuingdevelopment in efforts to develop injection devices and methods thatoffer benefits such as greater comfort and less pain while providingeffective subcutaneous injection.

SUMMARY

Recognized herein is a need for new and/or improved apparatuses, systemsand methods for injection of medicaments (e.g., drugs) from a reservoir,e.g., source vial or vials, to and into a subject. Further, recognizedherein is a need for apparatuses, systems, and methods for monitoring ahealth or physiologic parameter prior to, during, and/or followinginjection of a medicament into a subject. Such an apparatus or systemmay be useful, for example, in regulatory procedures and patientmonitoring.

The present disclosure provides apparatuses, systems, and methods thatmay be used for medical fluid transfer and injection, and methods foradministering a substance (e.g., medicament) to a subject and monitoringthe subject for one or more physical parameters or attributes before,during and/or after the administration of the substance.

In an aspect, provided herein is a system for measuring a health orphysiological parameter from a subject, comprising: (a) a patchcomprising a first housing having a sensor configured to: (i) measuresaid health or physiological parameter from said subject when said patchis secured to a body of said subject, and (ii) provide one or moreoutputs corresponding to said health or physiological parameter fromsaid subject, wherein said first housing comprises an opening; and aninjector having a second housing comprising a cannula in fluidcommunication with a fluid flow path, wherein said second housing iscoupled to said first housing such that said cannula is directed throughsaid opening and in contact with a body of said subject when said patchis secured to said body, wherein said injector is configured to (i)direct a substance from a reservoir to said fluid flow path in fluidcommunication with said reservoir, and (ii) direct said substance fromsaid fluid flow path into said subject through said cannula.

In some embodiments, the system further comprises a pump integrated withthe cannula, wherein the pump is configured to direct the substance fromthe fluid flow path into the subject through the cannula. In someembodiments, the cannula is configured to extend towards or retract awayfrom the body of the subject. In some embodiments, the opening comprisesa pierce-able membrane. In some embodiments, the pierce-able membrane ispierced by the cannula to generate the opening. In some embodiments, thereservoir is secured to the injector. In some embodiments, the reservoiris removable from the injector. In some embodiments, the reservoir ispart of the injector. In some embodiments, the substance is amedicament. In some embodiments, the medicament is for treating one ormore diseases selected from the group of cardiovascular,musculoskeletal, gastrointestinal, dermatology, immunology,ophthalmology, hematology, neurology, oncology, endocrinology, metabolicand respiratory disease. In some embodiments, the injector comprises thereservoir, wherein the reservoir is configured to contain a formulationhaving the substance. In some embodiments, the first housing isremovably coupled to the second housing. In some embodiments, the patchcomprises a communication interface for transmitting data correspondingto the plurality of health or physiological parameters to an electronicdevice in communication with the communication interface. In someembodiments, the communication interface comprises a wirelesscommunication interface. In some embodiments, the communicationinterface comprises a Wi-Fi interface. In some embodiments, thecommunication interface comprises a near field communication interface.In some embodiments, the communication interface comprises a Bluetoothinterface. In some embodiments, the communication interface comprises anoptical wireless interface. In some embodiments, the communicationinterface comprises a direct electrical contact digital or analoginterface. In some embodiments, an input transducer/sensor of theplurality of sensors is selected from the group consisting of aconductivity sensor, impedance sensor, capacitance sensor, chargesensor, humidity sensor, temperature sensor, heart rate sensor,interstitial pressure sensor, resistance sensor, optical sensor,distension sensor, acoustic sensor, vibration sensor, blood pressuresensor, color sensor, chemical sensor, and a substance-tracking sensor.In some embodiments, the system further comprises a second sensor,wherein the second sensor is configured to measure one or more deviceparameters chosen from the group consisting of: a dosage of thesubstance that is administered, a flow rate of dispensing of thesubstance, a volume of the substance that is administered, an occlusionof the cannula, and contact of the cannula into the body of the subject.In some embodiments, the patch or the injector comprises the secondsensor. In some embodiments, the patch further comprises one or moretransducers. In some embodiments, the one or more transducers isconfigured to generate an output signal, wherein the output signalcomprises a vibration signal, audio signal, or visual signal. In someembodiments, an output transducer of the plurality of transducers isselected from the group consisting of a haptic(vibration) transducer,audio transducer, visual transducer, and direct electrical stimulation(e.g. transcutaneous electrical nerve stimulation/TENS).

In another aspect, disclosed herein is a method for measuring aplurality of health or physiological parameters from a subject,comprising: (a) providing: (i) a patch comprising a first housing havinga plurality of sensors and comprising an opening, and (ii) an injectorhaving a second housing comprising a cannula in fluid communication witha fluid flow path, wherein the second housing is coupled to the firsthousing of the patch, and wherein the injector comprises a reservoircomprising a substance and a fluid flow path in fluid communication withthe reservoir; (b) securing the patch to a body of the subject; (c) whenthe patch is secured to the body of the subject, directing the cannulathrough the opening to (i) direct the substance from the reservoir tothe fluid flow path, and (ii) direct the substance from the fluid flowpath into the subject through the cannula; and (d) using the pluralityof sensors to (i) measure the plurality of health or physiologicalparameters from the subject, and (ii) provide one or more outputscorresponding to the plurality of health or physiological parametersfrom the subject.

In some embodiments, the method further comprises using a pumpintegrated with the cannula to direct the substance from the fluid flowpath into the subject through the cannula. In some embodiments, thecannula is configured to extend towards or retract away from the body ofthe subject. In some embodiments, the opening comprises a pierce-ablemembrane. In some embodiments, the pierce-able membrane is pierced bythe cannula to generate the opening. In some embodiments, the reservoiris secured to the injector. In some embodiments, the reservoir isremovable from the injector. In some embodiments, the reservoir is partof the injector. In some embodiments, the substance is a medicament. Insome embodiments, the medicament is used for treating one or morediseases selected from the group of cardiovascular, musculoskeletal,gastrointestinal, dermatology, immunology, ophthalmology, hematology,neuroscience, oncology, endocrinology, metabolic and respiratorydisease. In some embodiments, the injector comprises the reservoir,wherein the reservoir is configured to contain a formulation having thesubstance. In some embodiments, the first housing is removably coupledto the second housing. In some embodiments, the patch comprises acommunication interface for transmitting data corresponding to theplurality of health or physiological parameters to an electronic devicein communication with the communication interface. In some embodiments,the communication interface is a wireless communication interface. Insome embodiments, the communication interface is a Wi-Fi interface. Insome embodiments, the communication interface is a near fieldcommunication interface. In some embodiments, the communicationinterface is a Bluetooth interface. In some embodiments, thecommunication interface is an optical wireless interface. In someembodiments, an input transducer/sensor of the plurality of sensors isselected from the group consisting of a conductivity sensor, impedancesensor, capacitance sensor, charge sensor, humidity sensor, temperaturesensor, heart rate sensor, interstitial pressure sensor, resistancesensor, distension sensor, acoustic sensor, vibration sensor, bloodpressure sensor, color sensor, chemical sensor, and a substance-trackingsensor. In some embodiments, an output transducer of the plurality oftransducers is selected from the group consisting of a haptic(vibration)transducer, audio transducer visual transducers, and direct electricalstimulation (e.g. transcutaneous electrical nerve stimulation/TENS).

In some embodiments, a second sensor of the plurality of sensors isselected from the group consisting of temperature sensor, humiditysensor, flow rate sensor, button position sensor, vibration sensor,audible sensor, skin sensor.

In yet another aspect, provided herein is an injector comprising; (a) ahousing; (b) a medicament reservoir provided in the housing; (c) aninjection cannula moveable within the housing between a pre-dispenseposition and a dispense position in fluid communication with thereservoir; (d) an injector transducer/sensor mounted on or within thehousing; (e) a skin attachment layer attached to the housing, the skinattachment layer including an adhesive configured to secure the housingto a user's skin with a first holding force; (f) a patch removablysecured to the housing with a second holding force, the patch includinga sensor adhesive layer configured to secure the patch to a user's skinwith a third holding force, a patch input transducer/sensor, outputtransducer and circuitry configured to receive data from the injectortransducer/sensor and the patch transducer/sensor and transmit receiveddata to a remote receiver; (g) wherein the third holding force isgreater than the second holding force.

In some embodiments, the second holding force is greater than the firstholding force and the patch is removably attached to the skin attachmentlayer. In some embodiments, the patch is removably attached to the skinattachment layer by perforations. In some embodiments, the patch isremovably secured to the housing by a magnet. In some embodiments, amagnet is positioned within or on the housing of the injector and thepatch includes a metallic portion configured to be engaged by themagnet. In some embodiments, the skin attachment layer includes anopening and the patch is positioned within the opening when it isremovably secured to the housing of the injector. In some embodiments,the opening is centrally located in the skin attachment layer and theinjection cannula of the injector passes through the opening of the skinattachment layer and an orifice of the patch when in the dispenseposition. In some embodiments, the patch includes an extension includingthe orifice through which the injection cannula of the injector passeswhen in the dispense position, the extension configured to compress auser's skin around an injection site. In some embodiments, the patchincludes a printed circuit board upon which the circuitry is positionedand to which the sensor adhesive layer and the patch transducer/sensorare attached, the sensor adhesive layer including a central windowthrough which the extension passes.

In some embodiments, the extension is generally conical shaped. In someembodiments, the patch includes a printed circuit board upon which thecircuitry is positioned and to which the sensor adhesive layer and thepatch sensor are attached. In some embodiments, the circuitry of thepatch includes a microcontroller/microprocessor and a transmitter. Insome embodiments, the sensor of the injector includes a transmitter andthe circuitry of the patch further includes a receiver through whichdata is received from the injector transducers/sensors by wirelesstransmission and through which data is sent to transducers throughwireless transmission. In some embodiments, themicrocontroller/microprocessor, transmitter and receiver are combinedinto a single component. In some embodiments, the injector furthercomprises a wire connection between the injector transducers/sensor andthe circuitry of the patch, the wire connection configured to disconnectas or after the injector is removed from the patient. In someembodiments, the microcontroller/microprocessor and the transmitter arecombined into a single component. In some embodiments, the transmitteris a Bluetooth transmitter. In some embodiments, the injector sensorincludes a plurality of input transducers/sensors and outputtransducers. In some embodiments, the patch sensor includes a pluralityof input transducers/sensors and output transducers. In someembodiments, the patch sensor includes a plurality of either inputtransducers/sensors and output transducers.

In yet another aspect, provided herein is a method for collecting datafrom an injector and a patient comprising (a) attaching an injectorincluding an injector sensor and a patch including a patch sensor,output transducers and circuitry to the patient; (b) receiving data fromthe injector sensor and the patch sensor using the patch circuitry; (c)transmitting the received data to a remote receiver using the patchcircuitry; (d) removing the injector from the patient; (e) receivingadditional data from the injector sensor using the patch circuitry afterremoval of the injector from the patient; and (f) transmitting theadditional received data to a remote receiver using the patch circuitry.

In some embodiments, the injector and the patch are attached to thepatient simultaneously. In some embodiments, (a) includes attaching thepatch before the injector and, before attaching the injector to thepatient, further comprising the steps of receiving data from the patchsensor using the patch circuitry transmitting the received data to aremote receiver using the patch circuitry. In some embodiments, the datacollected from the patient includes measurable attributes that may beaffected by a drug administered by the injector and/or injection of thedrug using the injector. In some embodiments, the data collected fromthe patient includes measurable attributes that may affect or areindicators of the safety and/or efficacy of a drug administered by theinjector and/or use of the injection.

In yet another aspect, provided herein is a method for monitoring aninjection site of a patient for an injection site reaction comprisingthe steps of: (a) attaching an injector including a patch including apatch sensor and circuitry to the patient, where the patch sensorincludes a skin temperature transducer/sensor and a skin color monitor;(b) receiving data from patch sensor using the patch circuitry; (c)transmitting the received data to a remote receiver using the patchcircuitry, wherein the data includes an indication of temperature riseor change in skin color so that an injection site reaction may beidentified.

In another aspect, disclosed herein is an injector comprising (a) ahousing; (b) a medicament reservoir provided in the housing; (c) aninjection cannula moveable within the housing between a pre-dispenseposition and a dispense position in fluid communication with thereservoir; (d) a patch sensor configured to receive and transmit data,the patch sensor removably secured to the housing with a first holdingforce; (e) an attachment layer attached to the patch sensor, theattachment layer including an adhesive configured to secure the patchsensor to a user's skin with a second holding force; (f) wherein thesecond holding force is greater than the first holding force so that thepatch sensor remains attached to the user's skin as the housing isremoved from the patch sensor.

In some embodiments, the body of the subject is skin. In someembodiments, the patch is configured to receive data from the injector.In some embodiments, the data is used to adjust a device parameter ofthe patch or the injector. In some embodiments, the device parametercomprises one or more device parameters selected from the groupconsisting of a dosage of the substance that is administered by theinjector, a flow rate of dispensing of the substance of the injector,and a volume of the substance that is administered by the injector. Insome embodiments, the data is used to generate a notification to thesubject via a transducer. In some embodiments, the notificationcomprises one or more notifications selected from the group consistingof: a vibration, a sound, direct electrical stimulation, and a visualindicator.

There are several aspects of the present subject matter which may beembodied separately or together in the devices and systems described andclaimed below. These aspects may be employed alone or in combinationwith other aspects of the subject matter described herein, and thedescription of these aspects together is not intended to preclude theuse of these aspects separately or the claiming of such aspectsseparately or in different combinations as set forth in the claimsappended hereto.

The present subject matter includes a transfer device and/or an injectorof any suitable detailed construction but transfer and injectors thatare particularly useful in combination with the apparatus here aredescribed in U.S. Pat. No. 9,925,333, the contents of which are herebyincorporated by reference herein.

In an aspect, an injector includes a housing. A medicament reservoir isprovided in the housing and an injection cannula is moveable within thehousing between a pre-dispense position and a dispense position in fluidcommunication with the reservoir. An injector sensor is mounted on orwithin the housing. A skin attachment layer is attached to the housingand includes an adhesive configured to secure the housing to a user'sskin with a first holding force. A patch is removably secured to thehousing with a second holding force and includes a sensor adhesive layerconfigured to secure the patch to a user's skin with a third holdingforce. The third holding force is greater than the second holding force.The patch also includes a patch sensor and circuitry configured toreceive data from the injector sensor and the patch sensor and transmitreceived data to a remote receiver.

In another aspect, a process is provided for collecting data from aninjector and a patient includes the steps of: attaching an injectorincluding an injector sensor and a patch including a patch sensor andcircuitry to the patient; receiving data from the injector sensor andthe patch sensor using the patch circuitry; transmitting the receiveddata to a remote receiver using the patch circuitry; removing theinjector from the patient; receiving additional data from the injectorsensor using the patch circuitry after removal of the injector from thepatient; and transmitting the additional received data to a remotereceiver using the patch circuitry.

In still another aspect, a process for monitoring an injection site of apatient for an injection site reaction includes the steps of: attachingan injector including a patch including a patch sensor and circuitry tothe patient, where the patch sensor includes a skin temperature sensorand a skin color monitor; receiving data from patch sensor using thepatch circuitry; and transmitting the received data to a remote receiverusing the patch circuitry, wherein the data includes an indication oftemperature rise or change in skin color so that an injection sitereaction may be identified.

In still another aspect, an injector includes a housing with amedicament reservoir provided in the housing. An injection cannula ismoveable within the housing between a pre-dispense position and adispense position in fluid communication with the reservoir. A patchsensor configured to receive and transmit data is removably secured tothe housing with a first holding force. A skin attachment layer isattached to the patch sensor and is configured to secure the patchsensor to a user's skin with a second holding force, where the secondholding force is greater than the first holding force.

Another aspect of the present disclosure provides a non-transitorycomputer readable medium comprising machine executable code that, uponexecution by one or more computer processors, implements any of themethods above or elsewhere herein.

Another aspect of the present disclosure provides a system comprisingone or more computer processors and computer memory coupled thereto. Thecomputer memory comprises machine executable code that, upon executionby the one or more computer processors, implements any of the methodsabove or elsewhere herein.

Additional aspects and advantages of the present disclosure will becomereadily apparent to those skilled in this art from the followingdetailed description, wherein only illustrative embodiments of thepresent disclosure are shown and described. As will be realized, thepresent disclosure is capable of other and different embodiments, andits several details are capable of modifications in various obviousrespects, all without departing from the disclosure. Accordingly, thedrawings and description are to be regarded as illustrative in nature,and not as restrictive.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.To the extent publications and patents or patent applicationsincorporated by reference contradict the disclosure contained in thespecification, the specification is intended to supersede and/or takeprecedence over any such contradictory material.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings (also “Figure” herein), of which:

FIG. 1 shows a perspective view of an injector.

FIG. 2 shows a top view of a filled injector showing the deliveryindicator in a full state.

FIG. 3 shows top view of a filled injector showing the deliveryindicator in an empty state.

FIG. 4 shows a perspective view showing the underside of the injectorwith attached tape and fill port.

FIG. 5 shows a perspective view showing the underside of the injectorwith tape detached and the fill and dispense ports exposed.

FIG. 6 shows a cross-section of the injector on the transfer apparatus.

FIG. 7 shows a perspective view of the injector attached to the body(e.g., skin) with the safety device installed.

FIG. 8 shows a perspective view of the injector attached to the body(e.g., skin) with the safety device removed and the button up in apre-fire state.

FIG. 9 shows a perspective view of the injector attached to the body(e.g., skin) with the safety device removed and the button down in afired state.

FIG. 10 shows a cross-section view of the injector attached to the body(e.g., skin) with the button up in a pre-fire state.

FIG. 11 shows a cross-section view of the injector attached to the body(e.g., skin) with button down in a first fired state.

FIG. 12 shows a cross-section view of the injector attached to the body(e.g., skin) with button down in a dispense state.

FIG. 13 shows a cross-section view of the injector attached to the body(e.g., skin) showing the end of delivery indicator not triggered.

FIG. 14 shows a cross-section view of the injector attached to the body(e.g., skin) showing the end of delivery indicator triggered.

FIG. 15 shows a cross-section view of the injector attached to the body(e.g., skin) with button locked up in a post-fired state.

FIG. 16 shows a perspective view of the injector removed from the body(e.g., skin) with the bandage remaining on the skin. FIG. 16B shows aperspective view of the injector removed from the body (e.g., skin) withthe bandage, comprising an opening, remaining on the skin.

FIG. 17 shows a perspective view of the injector with the top housingremoved in a filled state.

FIG. 18 shows a top view of the injector shown in FIG. 17.

FIG. 19 shows a perspective view of the injector with the top housingremoved in an empty state.

FIG. 20 shows a top view of the injector shown in FIG. 19.

FIG. 21 shows a perspective view of the injector placed on the body(e.g., skin) and the safety in place.

FIG. 22 shows a perspective view of the injector placed on the body(e.g., skin) and the safety removed.

FIG. 23 shows a perspective view of the injector placed on the body(e.g., skin) and the button depressed to fire start the injection.

FIG. 24 shows a perspective view of the injector removed from the body(e.g., skin) after the injection with the button in a locked positionand a bandage remaining on the body (e.g., skin).

FIG. 25 shows a perspective view of an injector.

FIG. 26 shows a cross-section of FIG. 25 showing the injector with thebutton in the first position.

FIG. 27 shows an illustration (Van Gerwen, D. J. Cannula-TissueInteraction by Experiment. Ph.D. Thesis, Delft University of Technology,2013. ISBN 978-94-6186-238-9, pg. 11) showing four stages of cannulapenetration into tissue including a) no contact, b) boundarydisplacement, c) tip insertion and d) shaft insertion.

FIG. 28 shows a cross-section of FIG. 25 showing an injector with thebutton in a second position or dispense position.

FIG. 29 shows a cross-section of FIG. 25 showing adhesive/device andadhesive/body (e.g., skin) interfaces.

FIG. 30 shows a perspective view of the bottom of an injector showingthe different zones of the adhesive.

FIG. 31 shows a cross-section of FIG. 25 showing bulging tissue on adevice with permanently attached adhesive.

FIG. 32 shows a cross-section of FIG. 25 showing bulging tissue on adevice with multi-zone attached adhesive.

FIG. 33 shows a perspective view of the top of an alternative injector.

FIG. 34 shows a cross-section of FIG. 33 showing a dislodgment sensornon-engaged and the cannula locked in the dispense position.

FIG. 35 shows a cross-section of FIG. 33 showing a dislodgment sensorengaged and the cannula and button retracted to post-fire position.

FIG. 36 shows a cross-section of FIG. 25 showing an injector with thebutton in the first position or pause position.

FIG. 37 shows a cross-section of FIG. 25 showing an injector with thebutton in a second position or dispense position.

FIG. 38 shows a cross-section of FIG. 25 showing an injector with thecannula retracted and the button in the up or pre-fire position.

FIG. 39 shows a cross-section of FIG. 25 showing an injector with thebutton in a second position or dispense position.

FIG. 40 shows a perspective view of an injector.

FIG. 41 shows a cross-sectional perspective of an injector with thebutton in a second position or dispense position.

FIG. 42 shows a perspective view of an injector with the attached safetysleeve.

FIG. 43 shows a cross-sectional perspective of an injector with thebutton in second position or dispense position.

FIG. 44 shows a perspective view of an injector including aradiofrequency (RF) tag and a tag reader or interrogator.

FIG. 45 shows similar to FIG. 44 but shows the injector in crosssection.

FIG. 46 shows a block diagram/flow chart, illustrating a systememploying the present subject matter for monitoring patient compliance.

FIG. 47 shows an ultrasound image showing the subcutaneous depth of abolus injection employing a commercial infusion pump with a 9 mmsubcutaneous cannula depth.

FIG. 48 shows an ultrasound image showing the depth of a bolus injectionemploying injector 7 with a 5 mm cannula depth.

FIG. 49 depicts a compliance monitoring system.

FIG. 50 further depicts a compliance monitoring system.

FIG. 51 shows additional aspects of a compliance monitoring with aninjector of the type described herein.

FIG. 52 shows a top perspective view of a RF chip in an embodiment ofthe injector of the disclosure.

FIG. 53 shows a bottom perspective view of the RF chip of an embodimentof the present disclosure.

FIG. 54 shows a top perspective view of an embodiment of the injector ofthe disclosure with a safety tab installed.

FIG. 55 shows a top perspective view of the injector with the safety tabremoved.

FIG. 56 shows a cross-sectional view of the injector showing the pushbutton in the raised, extended, or up position.

FIG. 57 shows a cross-sectional view of the injector showing the pushbutton in the lowered, retracted or down position.

FIG. 58 shows a flow chart showing processing performed by amicrocontroller/microprocessor in an embodiment of the injector of thedisclosure.

FIG. 59 shows bottom perspective view of an injector with detachablepatch in an embodiment of the disclosure.

FIG. 60 shows an exploded view of the injector and patch of FIG. 59.

FIG. 61 shows a top side perspective view of the printed circuit board(PCB) chip of the patch of FIG. 60.

FIG. 62 shows a bottom side perspective view of the PCB chip of thepatch of FIG. 60.

FIG. 63 shows a schematic of the injector and patch of FIGS. 59-63.

FIG. 64 shows a schematic of another example of an injector coupled to apatch.

FIG. 65 shows another view of the patch and injector shown in FIG. 64.

FIG. 66 shows a schematic of another example of an injector coupled to apatch.

FIG. 67 shows a schematic of another example of an injector coupled to apatch.

FIG. 68 shows a cross-sectional view of the patch and injector of FIG.67.

FIG. 69 shows a schematic of another example of an injector coupled to apatch.

FIG. 70 shows a cross-sectional view of the patch and injector of FIG.69.

FIG. 71 shows a schematic of another example of an injector coupled to apatch.

FIG. 72 shows a cross-sectional view of the patch and injector of FIG.71.

FIG. 73 shows a schematic of another example of an injector coupled to apatch.

FIG. 74 shows a cross-sectional view of the patch and injector of FIG.73.

FIG. 75 shows a schematic of another example of an injector coupled to apatch.

FIG. 76 shows a schematic of another example of an injector coupled to apatch.

FIG. 77 shows a schematic of another example of an injector coupled to apatch.

FIG. 78 shows a cross-sectional view of the patch and injector of FIG.77.

FIG. 79 shows a schematic of another example of an injector coupled to apatch.

FIG. 80 shows a schematic of another example of an injector coupled to apatch.

FIG. 81 shows a cross-sectional view of the patch and injector of FIG.80.

FIG. 82 shows a schematic of another example of an injector coupled to apatch.

FIG. 83 shows a cross-sectional view of the patch and injector of FIG.82.

FIG. 84 shows a schematic of another example of an injector coupled to apatch.

FIG. 85 shows a cross-sectional view of the patch and injector of FIG.84.

FIG. 86 shows a schematic of another example of an injector coupled to apatch.

FIG. 87 shows a cross-sectional view of the patch and injector of FIG.86.

FIG. 88 shows a schematic of another example of an injector coupled to apatch.

FIG. 89 shows a cross-sectional view of the patch and injector of FIG.88.

FIG. 90 shows a schematic of an example patch with a pierceable membraneconfigured to couple to an injector.

FIG. 91 shows another view of the patch from FIG. 90.

FIG. 92 shows a schematic of another example patch with a pierceablemembrane configured to couple to an injector.

FIG. 93 shows a schematic of an example patch with a pierceable membraneconfigured to couple to an autoinjector.

FIG. 94 shows a schematic of an embodiment of a patch sensor of theinjector and patch of any of FIGS. 59-93.

FIG. 95 shows a schematic of the sensor adhesive layer of the patch inan alternative embodiment of the disclosure.

FIG. 96 shows a schematic of sensor adhesive layers of the patch in anembodiment of the present disclosure.

FIG. 97 schematically illustrates an example workflow of a mobileapplication.

FIG. 98 schematically illustrates another example workflow of a mobileapplication.

FIG. 99 schematically illustrates another example workflow of a mobileapplication. FIG. 99A shows a schematic. FIG. 99B shows anotherschematic. FIG. 99C shows yet another schematic.

FIG. 100 shows a computer system that is programmed or otherwiseconfigured to implement methods provided herein.

DETAILED DESCRIPTION

While various embodiments of the invention have been shown and describedherein, it will be obvious to those skilled in the art that suchembodiments are provided by way of example only. Numerous variations,changes, and substitutions may occur to those skilled in the art withoutdeparting from the invention. It should be understood that variousalternatives to the embodiments of the invention described herein may beemployed.

Whenever the term “at least,” “greater than,” or “greater than or equalto” precedes the first numerical value in a series of two or morenumerical values, the term “at least,” “greater than” or “greater thanor equal to” applies to each of the numerical values in that series ofnumerical values. For example, greater than or equal to 1, 2, or 3 isequivalent to greater than or equal to 1, greater than or equal to 2, orgreater than or equal to 3.

Whenever the term “no more than,” “less than,” or “less than or equalto” precedes the first numerical value in a series of two or morenumerical values, the term “no more than,” “less than,” or “less than orequal to” applies to each of the numerical values in that series ofnumerical values. For example, less than or equal to 3, 2, or 1 isequivalent to less than or equal to 3, less than or equal to 2, or lessthan or equal to 1.

The term “subject,” as used herein, generally refers to a user of adevice, system, or method of the present disclosure, or an individual onwhich a device, system, or method of the present disclosure is beingused. The subject may be a patient (e.g., a patient that is beingtreated or monitored by a physician or healthcare provider). As analternative, the subject may not be a patient. The subject may have orbe suspected of having a disease or disorder. As an alternative, thesubject may be asymptomatic with respect to a disease or disorder. Thesubject may be a vertebrate, a mammal (e.g., human or animal), anon-human primate, etc. The subject may be an animal, such as a rodent(e.g., rat or mouse), a canine (e.g., dog), a feline (e.g., cat), abovine, or other animal.

The term “medicament,” as used herein, generally refers to a substancethat is used for treating a health or physiological state or conditionof a subject (e.g., medical treatment). The medicament may be a drug ortherapeutic agent. The medicament may be a solid, liquid, gas, orcombinations thereof. The medicament may be an aerosol, pill, tablet,capsule, pastille, elixir, emulsion, effervescent powder, solution,suspension, tincture, liquid, gel, dry powder, vapor, droplet, ointment,or a combination or variation thereof. A medicament may be used to treatan illness, ailment, or disease, or may be used as a health supplement(e.g., vitamins, minerals, probiotics, etc.).

The present disclosure provides devices, methods and systems fordelivering a substance (e.g., a medicament) to a subject and monitoringthe subject prior to, concurrently with and/or subsequent to deliveringthe substance. A device of the disclosure may be an injector thatdelivers the medicament. Alternatively, or in addition to, the devicemay be a patch that is configured to monitor the subject and/orcommunicate with the injector. In some examples, the injector and patchare separate devices (e.g., separable from each other). As analternative, the injector and patch may be part of single device (e.g.,not separable from each other).

Injector

Referring to FIG. 1, the injector 7 may be of any suitableconfiguration. As explained earlier, the injector may advantageouslyemploy one or more of the features of the injectors described in U.S.Pat. No. 9,925,333, the contents of which are hereby incorporated byreference herein.

Referring to FIGS. 1-3, the injector 7 has a generally low-profile,disc-shaped outer housing 74 with an upper surface 75 and a lowersurface 76, through which a cannula or needle protrudes when actuated bythe user. The upper surface 75 has an actuator or button 77 to start theinjection and a section 80 of the housing 74 that allows the subject ormedical professional to view the expandable member 78 to ascertain theamount of a substance 79, e.g., injectable fluid or medicament, in thein a reservoir of injector 7. In such cases, the section 80 of thehousing may comprise a transparent material, and the user coulddetermine whether the injection has commenced or concluded. In somecases, the expandable member 78 and/or the section 80 of the housing 74may be graduated, such as by demarcations 127 or the like, so that thesubject or a medical professional can visually determine the amount ofsubstance 79 remaining with greater precision—such as, for example,about 50% complete or about 75% complete. In addition, the expandablemember 78 may itself include or interact with a feature on the outerhousing 74 to show the amount of substance 79 remaining in the reservoirof the injector. For example, when the injector 7 is full of substance79, the clear section 80 may show one color such as but not limited togreen. When the injector 7 is empty of substance 79, the clear section80 may show a different color such as but not limited to red. In themiddle of dispense, the clear section 80 could show a combination ofcolors.

Referring to FIGS. 4-6, the undersurface 76 of the injector 7 includes afilling port 81 and a dispense port 82. The filling port 81 is theinterface that allows the transfer apparatus filling tube 83 to transfersubstance 79 to the injector 7 (e.g., a reservoir of the injector). Thedispense port 82 also contains an internal pathway 84 between theexpelled substance 79 from the expandable member 78 and the cannula 85.The filling port 81 and dispense port 82 may be in direct fluidcommunication through internal pathways 86, or they may be combined intoa single port.

Referring to FIGS. 4-6, the injector may include a filling port 81 thatincludes a check valve 87 to prevent pressurized substance 79 fromleaking out of the injector 7 when the injector 7 is removed from thetransfer apparatus 6 and the filling port 81 is removed from the fillingtube 83.

Referring to FIGS. 4-6, the injector 7 may also have a filling port 81that is configured to accept the insertion of a syringe. This syringemay be configured with a luer fitting or a cannula. This filling port 81configuration allows for the manual filling of the injector by the user.The transfer apparatus 6 may still be used but would not be required inthis configuration.

Referring to FIGS. 4-26, the injector 7 may also have a dispense port 82that is configured to directly connect to a cannula via attached tubingor a standard cannula port.

Referring to FIGS. 4-6, the undersurface 76 of the injector 7 carries anadhesive 88 for securing the injector 7 temporarily to a body (e.g., theskin) of a subject until the injection is complete. During removal ofthe injector 7, an adhesive tape liner 89 may be removed automaticallyexposing an adhesive surface 88 on the undersurface 76 of the injector 7that may be used to adhere the injector 7 to the patient's body (e.g.,skin). Alternatively, the tape liner 89 may have a tab 90 that the userpulls to manually remove before adhering the injector 7 to the skin.Alternatively this tab may be attached to the surface of the transferdevice 4 so that the tape liner is automatically removed upon removal ofthe injector 7.

Referring to FIGS. 4-6, the injector 7 may have an adhesive tape flange91 that extends beyond the undersurface base 76. This flange 91 ofadhesive tape 88 can act as a strain relief between the injector 7 andskin surface, reducing the risk of accidentally dislodging the injector7 from the skin. In other words, similar to a tapered strain relief on awire where it enters into a connector, the extended adhesive flange 91acts to distribute the load on both sides of the connection pointbetween the adhesive tape 88 and the undersurface base 76 of theinjector 7 to reduce any stress risers at the adhesive tape 88 and skininterface.

Referring to FIGS. 4-6, the injector 7 may be configured with a taperedunderside surface 98 that presses on the adhesive flange 91 to securelyattach the adhesive tape 88 to the skin as the user is securing theinjector 7 to the skin without additional user intervention. By usingthe compliance of a person's skin when pressing the injector 7 againstthe skin, the tapered underside surface 98 of the injector 7 effectivelypresses the flange 91 of the adhesive tape 88 against the skin but theupper exposed surface of the flange 91 portion does not have exposedadhesive and therefore is not attached to that portion of the taperedunderside surface 98. The user is not required to run their fingeraround the flange 91 to secure the injector 7 to the skin making it amuch simpler method of adhesive tape 88 attachment.

Referring to FIGS. 4-6, the injector 7 may have an underside surface 76that is flexible or compliant in lieu of being rigid to allow forimproved attachment by conforming of the injector 7 to the skin duringapplication.

Referring to FIGS. 7-9, after the injector 7 is placed against oradhered to the body (e.g., skin) 99 of the subject, a safety mechanismor lock-out mechanism may be automatically released and the injector 7is ready to fire (inject). In such cases, the injector 7 is preventedfrom being actuated (it is locked out) until it is placed against theskin. Alternatively, the user may manually remove a safety 100 such as asafety pin, safety sleeve, tab, or collar to release the injector to beready to fire (to inject, or to direct the cannula through the openinginto the subject). The injector 7 in some instances cannot be fireduntil the safety mechanism 100 is released. The safety mechanism 100 maybe passive or active and manually triggered by the user or automaticallytriggered by the injector 7.

Referring to FIGS. 7-9, the injector 7 may use an actuator or button 77and a visual indicator 101 in combination to indicate a parameter of theinjector 7 after it has been removed from the transfer apparatus. Forexample, when the button 77 is in the up position and the indicator 101has one color such as but not limited to green, this may indicate thatthe injector 7 is ready to start the injection. Additionally, the button77 may have a side wall 102 that is a different color from its top 103.When the button 77 is depressed, the user cannot see the sidewall 102 ofthe button 77; this may indicate that the injector 7 is in use. Theinjector 7 may alert the user when the injection of the drug iscompleted. This alert could be in the form of visual indicators, audiblesounds, mechanical movements or a combination. The button 77 is ideallydesigned to give the subject or user audible, visual and tactilefeedback when the button 77 ‘pops up’ into the locked-out position. Theinjector 7 may indicate to the subject that it is has completeddispensing and the full dose has been delivered to the patient with thebutton 77 in the up position and indicator window 101 showing theinjector reservoir is empty. For example, when the button 77 is in theup position and indicator 101 shows a different color such as but notlimited to red, this may indicate that the injector 7 has completed theinjection.

Referring to FIGS. 10-12, the injector 7 may have an actuator or button77 that the subject or user depresses on the injector 7 to start theinjection. The button 77 may be configured to be an on/off switch, i.e.,to only have two states, open and closed such as a light switch. Thismay prevent the user from pushing the button 77 half way and notactuating the injector 7. Once activated, this ‘light switch’ typebutton 77 would direct the cannula 85 rapidly into the skin 99,independent of the user manipulation of the button 77. Alternatively,the button 77 could have a continuous motion, allowing the user toslowly direct the cannula 85 into skin 99. The button 77 may preferablybe directly coupled to the cannula 85 by using adhesive 104 creating abutton 77 and cannula 85.

Referring to FIGS. 10-12, the injector 7 may have a cannula 85 that,when the injector 7 is coupled to the skin and upon actuation, directsthe substance from the reservoir to a fluid flow path in fluidcommunication with the reservoir, thereby directing the substance fromthe reservoir into the skin 99. Upon actuation of the button 77 thatinitially goes to a first position or depth as shown in FIG. 11 andretracts slightly to a second position of depth, in some casesautomatically, as shown in FIG. 12. The first depth shown in FIG. 11 isachieved from over travel of the button 77 during actuation. The firstdepth may be controlled by features 105 in the button 77 in directcontact with the base 106 of the injector 7. The final depth of thecannula 85 is suitable for subcutaneous injections. Alternatively, thefinal depth of the cannula 85 may be reduced for intradermal injections.Alternatively, the final depth of the cannula 85 may be increased forintramuscular injections. Upon reaching the first depth, the cannula 85retracts away from the body of the subject to a second depth as shown inFIG. 12. The retraction distance of the cannula to the second depth isin the range of 0.1-2 mm. This retraction feature is used, in suchcases, to prevent the cannula 85 from being blocked by tissue during theinitial insertion process. This tissue blockage could require a veryhigh pressure to overcome and prevent the injector 7 from delivering thedrug. The retraction of the cannula 85 from the first position to asecond position generates an open pocket ahead of the cannula tip 107allowing reduced pressure for initiation of flow of drug from thecannula 85. This reduced pressure for initiation of the flow of drugfrom the cannula is necessary, in some instances, for the injector 7 tomaintain a relatively constant pressure, to direct the substance throughthe cannula during injection.

Referring to FIGS. 10-12, the injector 7 may include a cannula 85 with aside opening 108. As shown in FIG. 12, once the button 77 on theinjector 7 is fully depressed, the cannula 85 will be fully insertedinto the skin 99 through the dispense port 82 and the injector 7 willbegin dispensing of the substance. Until the button 77 is fullydepressed, the side-hole 108 and therefore the internal lumen of thecannula 85 is not in communication with the fluid channel 86 of thedispense port 82. Both the side-opening 108 and cannula-tip 107 areretained within a septum 109. With the side-opening 108 and cannula-tip107 being retained within the septum 109, the entire drug path is keptsterile until the time of use. When the button 77 is fully depressed andthe cannula 85 is in the dispense position, the side opening 108 in thecannula 85 is in communication with the fluid channel 86 of the dispenseport 82 and the injection of the substance (e.g., injectable medicamentor fluid) begins.

Referring to FIGS. 10-12, the septum 109 provides the advantage ofsealing the cannula tip 107 as well as the side opening 108 from theinjectable before and after dispensing. Sealing the cannula tip 107 andthe side opening 108 of the cannula 85 at the end of the injection has aparticular advantage to prevent dripping of the substance (e.g.injectable liquid) from the injector 7 after end of dispense and/orafter it is removed from the skin surface. It also prevents contaminatesfrom entering the hollow cannula prior to being actuated into the skin.The septum 109 may comprise a pierceable membrane that can be made ofany suitable material to allow for sealing once the cannula 85 haspunctured it. The material composition of septum 109, or of thepierceable membrane, may comprise silicone. Alternatively, the materialcomposition of the septum 109, or pierceable membrane, may also be ablend of different materials including but not limited to bromobutyl,chlorobutyl, isoprene, polyisoprene, SBR, polybudtadiene, EPDM, PTFE,natural rubber and silicone. Alternatively, the fluid pathway 86including the dispense port 82 could comprise a rigid plastic with asilicone injected overmold to produce the septum previously described.

Referring to FIGS. 10-12, the septum 109 at the dispense port 82 couldprotrude slightly from the underneath surface into the skin surface 99of the injector 7 to provide for pressure on the skin surface 99 at theinjection site. This pressure on the skin surface 99 by the dispenseport 82 after the cannula is retracted could eliminate the substancefrom coming out of the injection site commonly referred to as blowback.

Referring to FIGS. 10-12, the injector 7 may include a set of springtabs 110 that interface with the button 77 to perform locking functions.A spring tab 110 is biased to lock into an undercut 111 in the button 77to keep the button 77 in a first up position or pre-fire position asshown in FIG. 10. The geometry of the undercut 111 and spring tab 110help to produce the light switch actuation force described previously.This light switch actuation is accomplished by the translation of thebutton 77 relative to the spring tab 110 and the geometry of the matingundercut 111 surfaces.

Referring to FIGS. 10-12, the injector 7 may include a spring tab 112that interact with the button 77 in the injector 7 to perform lockingfunctions such that when the button 77 is actuated to the first depthand retracts slightly back to the second depth or dispense position,undercut features 113 in the button 77 allow a spring tab 112 to holdthe button 77 in the dispense position until the injector 7 hascompleted dispensing.

Referring to FIGS. 13-14, the injector 7 may include an end of deliveryindication or empty indicator 114 to sense when all of the substance(e.g., medicament or injectable fluid) has been expelled from theexpandable member 78 and the injector 7 has completed dispensing. Theempty indicator 114 may be configured with a slot or other opening 115to slide over the expandable member 78 at the exit port when theexpandable member 78 is in a deflated state after all of the substancehas been expelled. There may be two states of the empty indicator. Asshown in FIG. 13, the empty indicator may be in a first position ordeflected-out state when the expandable member 78 is full of thesubstance at that section and is not contained within the slot oropening 115. This first position would translate to a non-empty state ofthe expandable member 78 when the diameter of the expandable member 78is larger than its minimum due to residual substance contained within.As shown in FIG. 14, the empty indicator 114 may be in a second positionor deflected-in state when the expandable member 78 is partially orfully contained within the slot or opening 115. This second positionwould translate to an empty state of the expandable member 78 when thediameter is at a minimum.

Referring to FIGS. 13-14, the injector 7 may include an automaticcannula retraction mechanism at the end of dispense. This mechanismincludes a direct coupling between a spring tab 112, button undercutfeature 113 and the empty indicator 114, all previously mentioned. Whenthe expandable member 78 is filled with the substance (e.g., medicamentor injectable fluid) and the button 77 is depressed from a firstpre-fire position to a second dispense position as shown in FIG. 14,undercut features 113 in the button 77 allow a spring tab 112 to holdthe button 77 in the dispense position until the injector 7 hascompleted dispensing. This spring tab 112 may also be directly coupledto the empty indicator 114 which is naturally in the first position ordeflected-out state. The motion of depressing the button 77 to a secondposition or dispense position allows a post feature 116 in the button 77to provide a bias or pre-tension on the spring tab 112 to direct theempty indicator 114 to its second position or deflected-in state.However, since the expandable member 78 is initially full of substanceat a large diameter, the empty indicator 114 cannot move to the secondposition or deflected-in state as shown in FIG. 13. After the button 77is depressed, the substance starts to expel out of the expandable member78 through the cannula as previously mentioned. Once the expandablemember 78 has expelled all of the substance and is at a minimumdiameter, the empty indicator 114 (under pretension from the spring tab112) will move to the second position or deflected-in state as shown inFIG. 14. The spring tab 112 directly coupled to the empty indicator 114also moves with the empty indicator 114. This movement releases thespring tab 112 from the undercut feature 113 in the button 77 to allowthe button 77 (and cannula) to move up to a final position or post fireposition after the dispense is completed as shown in FIG. 15.

Referring to FIG. 15, lock out spring tabs 117 may also interact withthe button 77 in the injector 7 to perform locking functions such thatwhen the injection is complete the button 77 is released, and the button77 is urged up by the return spring 118 to a final up position orpost-fire position. The button height 77 relative to the top of theinjector 7 in the final up position or post-fire position (shown in FIG.15) may be higher than the pre-firing position (shown in FIG. 10). Theend of the lock out spring tabs 117 move out to the outer diametersurface 119 of the button 77 within the outer housing 74 to lock thebutton 77 in the up position or post-fire position and prevent thebutton 77 from being actuated again.

Referring to FIG. 15, the injector 7 may include a return spring 118that interacts with the button 77 to provide a bias to the button 77into a first up position or pre-fire position. When the button isactuated down to a second depth or dispense position, the return spring118 is compressed causing more of a bias or preload. At the end of thedispense period, the button 77 is unlocked from the second depth ordispense position (shown in FIG. 12) to move up to a final position orpost fire position after the dispense is completed as previouslymentioned. It is the bias of the return spring 118 that forces thebutton 77 up to a final position or post-fire position.

Referring to FIG. 15-16, upon removal of the injector 7 from the skin99, the injector 7 will preferably be locked out, preventingnon-destructive access to the cannula or reuse of the injector 7. Theinjector 7 may indicate to the user that the full dose has beendelivered. This indication could be in the form of a visual indictor,audible sound, mechanical movement or a combination.

Referring to FIG. 16, upon removal of the injector 7 from the skin 35, abandage 120 may release from the injector 7 and remain on the skinsurface 35. This can be affected by using an adhesive on the bandageportion that more strongly attaches the bandage to the skin than theadhesive that attaches the bandage to the injector 7. Thus when thehousing is lifted from the skin, the bandage 120 remains in place overthe injection site as described in U.S. Pat. No. 7,637,891 and U.S.patent application Ser. No. 12/630,996, which are incorporated byreference herein. The bandage 120 may comprise an opening 120 b (e.g.hole or slit in the center of the bandage), as shown in FIG. 16B.

Referring to FIGS. 36-39, the injector 7 may preferably include amanifold 121 that assembles to both the expandable member 78 and thefilling port 81 and dispensing ports 82 and provides direct fluidcommunication between the expandable member 78 and the filling 81 anddispensing 82 ports of the injector 7. The manifold 121 may beconfigured on the end that assembles to the expandable member 78 to belarge in diameter to facilitate filling and expelling all of thesubstance out of the expandable member 78 as previously discussed. Themanifold 121 may preferably include internal passageways 122 to allowfor fluid flow in and out of the expandable member 78. The manifold 121may be configured with a filter 123 in the injectable fluid pathway 122for filtering the substance to remove particulate before and after it isintroduced into the expandable member 78. The filter 123 may be amembrane, depth filter or other suitable filtration media that is ofsufficiently small pore size or effective pore size to removeobjectionable particulate, which may include but not be limited toundissolved substance in those situations where the substance isreconstituted by the transfer apparatus. The manifold 121 may also beconfigured with a filter 123 for the removal or air. Such an air removerfilter 123 may include a bubble trap, air gap, or other configuration inthe injectable fluid pathway 122 that removes air from the injectablefluid pathway 122 before it is introduced into the expandable member 78.This air remover filter 123 may be configured with a hydrophobic filteror a combination of hydrophobic and hydrophilic filters. A hydrophobicfilter would allow for the venting of air from the transfer apparatusbut not the passage of liquid. A hydrophilic filter would allow thepassage of liquid but not the passage of particulate or air. The airremover filter 123 may also have check valves to allow for venting oftrapped air. Alternately, the air remover and filters 123 may be locatedat any point in the fluid pathway from the filling port 81 to thecannula 85. For example, the most downstream point in the fluid pathwayis the distal end 128 of the expandable member 78. An internal mandrel124 may be connected to distal end 128 of the expandable member 78. Anair remover or filter 123 may be integrated into this downstream pointto allow for venting of trapped air during filling of the injector 7.Furthermore, the mandrel 124 could include a slot along its length thatis in communication with the downstream filter 123 to aid in the ventingof air during the filling process.

Referring to FIGS. 36-39, the injector 7 may include a resilientexpandable member 78 such as an elastomeric balloon or bladder. Thematerial composition of expandable member 78 may preferably be silicone.Alternatively, the material composition of the expandable member 78 mayalso be a blend of different materials including but not limited tobromobutyl, chlorobutyl, isoprene, polyisoprene, SBR, polybudtadiene,EPDM, PTFE, natural rubber and silicone. In addition, the expandablemember 78 may be coated to improve their surface properties. Coatingsmay include parylene, silicone, Teflon and fluorine gas treatments.Alternatively, the expandable member 78 may be made from a thermoplasticelastomer.

Referring to FIGS. 36-39, the injector 7 may include a resilientexpandable member 78 which the substance is transferred under pressure.This causes the expandable member 78 to enlarge and the resilience ofthe expandable member 78 creates a pressure which tends to expel thesubstance. The pressure chamber of the transfer apparatus describedpreviously (or such other pump or pressurizing means as may be employedin the transfer apparatus) transfers the substance to the injector 7under pressure. Introducing the substance into the expandable member 78under pressure causes it to stretch and expand both in diameter andlength. An example of this would be blowing up a long, skinny balloon.The volume range of the injector 7 may be 0.5 to 30 milliliters. Whenexpanded, the resilient expandable member 78 exerts an expulsionpressure in the range of 1 to 200 psi on the substance contained in theexpandable member 78 so that the injector 7 is ready to administer thesubstance automatically when triggered by the user by depression of thebutton as previously described. Thus, the transfer apparatus aspreviously described operates not only to transfer a measured amount ofsubstance (and if necessary mix, dilute and filter it) to the injector7, but also simultaneously charges or provides the motive pressure tothe injector 7 (by expanding the resilient expandable member 78) so thatthe injector 7 is ready to automatically dispense the substance underthe pressure exerted by the resilient expandable member 78 when actuatedby the user.

This aspect of the transfer apparatus (simultaneous transferring andcharging) is particularly beneficial. While the above applications showthe injector 7 in a pre-filled or charged condition for injection of thesubstance 79 when the injector 7 is actuated, the present disclosurecontemplates that the injector 7 can remain empty and the expandablemember 78 in a more relaxed and un-filled condition, i.e., in anon-charged or non-filled condition, until administration of thesubstance is required. Only then is the substance mixed or processed asnecessary and introduced into the injector 7, expanding the expandablemember 78 to a filled (charged) condition. In the present disclosure,the drug is stored in its original container closure (vial) until thetime of use. Because the substance will typically be injected withinseconds to hours after transfer from the vial into injector 7, shelflife and material compatibility of the drug with the materials in thefluid pathway within the injector 7 are not significant issues. Thechallenges and expense of designing an injector 7 and selectingmaterials for an extended shelf life of pre-filled injector 7 aresignificantly reduced.

Referring to FIGS. 36-39, the present subject matter may use features ofthe injector 7 described in the patent applications incorporated byreference herein as previously described. However, the expandable member78 employed in the injector 7 here may also preferably take the form ofan elongated balloon or bladder arranged, for example, in a planarhelical or spiral configuration as illustrated. As previously mentioned,the injector 7 includes a circular shaped outer housing 74 that has aspiral slot or recess 125 formed therein. The elongated balloon orbladder 78 rests in the slot 125, with one end for communicatingdirectly or indirectly with an injection cannula 85 through fluidpathways 122 and the other end for communicating directly or indirectlywith a dispense indicator 101. The elongated spiral configuration allowsthe balloon or bladder 78 to have substantial volume for such quantityof substance 79 as may be desired, while also contributing to thelow-profile configuration of the injector 7. In some cases, by utilizinga relatively long expandable member 78 with a large length to diameterratio, very high pressures and volumes can be achieved with a minimum offorces required. Additionally the volume of the expandable member 78 canbe changed by changing the filling length, without significantlyaltering the pressure/volume curves of the expandable member 78.

Referring to FIGS. 36-39, one of the other aspects that may be employedin the present subject matter is the use of an insert or plug or mandrel124 within the expandable member 78 to pre-stress the expandable member78 to a slightly expanded position when unfilled, so that when theexpandable member 78 expels the substance, it will contract or collapseto a condition where it is still stretched or stressed and continues toexert pressure on any fluid there within as shown in FIGS. 38 and 39.This better assures that all or substantially all of the substance isfully expelled from the injector 7. The mandrel or shaft 124 could be afluid filled expandable member if desired. This would allow for avariable size mandrel 124. Alternatively, the expandable member 78 couldhave a sufficiently small internal volume (small diameter) whenunstressed so that virtually all the substance is expelled without theneed for and internal mandrel or shaft 124. Additionally, the expandablemember 78 could be flattened/stretched by ‘wrapping’ it around a surfacewithin the injector such as a cylindrical wall 134. The pre-stresscreated in the expandable member 78 would act to eliminate any residualfluid volume remaining within.

There are a number of different ways to cause an expandable member 78 toexpand and/or contract in an arcuate manner as previously described.Referring back to FIG. 15, one way is to design the expandable member 78with a thicker wall cross section 126 in one area around thecircumference of the expandable member 78 that would cause theexpandable member 78 to expand in a circular fashion. Alternatively, aseparate element 126 could be affixed along the length of the expandablemember 78 to effectively stiffen the expandable member 78 in thatportion of the circumference that would cause the expandable member 78to expand in an arcuate manner. Referring back to FIG. 17, another wayis to use internal features such as slots or recesses 125 in the housing74 of the injector 7 to guide the expandable member 78 around a circularor spiral path. These features 125 could interact with the expandablemember 78 in a number of ways, the simplest being the outer shape of theexpandable member is constrained by a slot 125 in the housing 74 of theinjector 7. Friction between the expandable member 78 and the innersurfaces 125 of the housing 74 could be reduced by lubricating theoutside surface of the expandable member 78, or by inserting theexpandable member 78 within a low spring rate spring that would limitboth the friction and outer diameter of the expandable member 78 whilenot constraining the length.

Referring to FIGS. 36-39, the elongated expandable member 78 may bepreferably configured to expand along an arc with a predetermined tubediameter without the aid of walls or a guide within the injector.Referring back to FIG. 15, looking at a cross-section of the elongatedexpandable member 78, a thicker wall area 126 in a small portion of thecircumference of the expandable member 78 may be added to cause theelongated expandable member 78 to expand in an arc as previouslydescribed. The arcuate expandable member 78 grows in length due toincrease in pressure and volume there within; the thicker section 126deflects less than the thinner section.

Referring to FIG. 17, the arcuate expandable member 78 will expand inlength in an arc shape as to orient its heavy wall thickness zone 126 orless deflecting zone to the inside of the circle. Increasing the wallthickness 126 of the expandable member 78 within the small zone 126around the circumference will effectively continue to decrease theradius of the arc of the expandable member 78. The increase in wallthickness 126 may be achieved by molding or extruding it into thearcuate expandable member 78 or by bonding a strip of material to oneside 126 of the expandable member to cause that portion of the wall 126to lengthen at a slower rate, thereby causing the expandable member 78to expand in an arc shape as previously discussed.

Referring to FIG. 18, the distal end of the expandable member 78 couldbe affixed an element such as an indicator 101, which is constrained tofollow guide path within the inner surfaces 125 of the housing 74.Alternately, the expandable member 78 could be pre-stretched andflattened around a circular diameter inside the injector 7 such as wall134 so that there would be no change in expandable member length.Alternatively, a straight or curved mandrel 124 whose length is morethan the unstressed expandable member could be used to stretch theexpandable member into a circular shape within the injector 7 prior tofilling. Alternatively, the mandrel 124 could be used as a visualindicator to show the state of the injector 7 and the progress of theinjection. The mandrel 124 could be colored to allow it to be easilyviewed through the housing.

Referring to FIGS. 36-39, the substance is injected into the expandablemember 78 by the transfer apparatus and the expandable member 78 isexpanded to a certain outer diameter controlled by the configuration ofthe inner surfaces 125 of the housing 74. In this way, the entire lengthof the expandable member 78 can be filled with a known volume of drug,and the outer diameter is known at each lengthwise location along theexpandable member 78. It is desirable to have the expandable member 78fill and empty along its length in a controlled way, from one end to theother to encourage the expandable member 78 to completely empty, and toallow the easy and accurate measurement of substance in the expandablemember. To visually aid in determining how much substance is in theexpandable member 78, graduated markings could be printed on theexpandable member 78, like a syringe, to indicate the volume remainingin the expandable member 78. As previously described and referring toFIGS. 21-22, the expandable member 78 and housing 74 could be clear toallow the user to see the drug 74 and the volume remaining in theinjector 7. Alternatively, graduated markings 127 could be printed onthe housing 74 to indicate the volume remaining in the expandable member78.

Referring to FIGS. 36-39, in accordance with an aspect of this subjectmatter mentioned above, the substance can be expelled progressively fromthe distal end 128 of the elongated expandable member 78 toward theproximal end 129. The proximal end 129 of the expandable member isclosest to the dispensing cannula 82 or cannula. This allows the user tovisually ascertain or approximate the injection status visually alone orwith the aid of graduation markings 127 on the injection housing 74, thewindow 80 or the expandable member 78. Progressive expulsion may beachieved in a variety of ways. For example, the substance exits theexpandable member 78 at the manifold 121 at the proximal exit portsection 130 and is preferably located at the proximal end 129 of theelongated expandable member (e.g., balloon or bladder). The thickness ofthe wall of the expandable member 78 may be varied, uniformly orstepwise increased, along its length from the distal end 128 toward theproximal end 129. Due to restraint by the walls of the spiral channel125 in which the expandable member 78 resides, the expandable member 78would be inflated with substance to a substantially uniform diameteralong its length. However, the thicker wall at the distal end 128 of theexpandable member 78 would exert greater contraction force on thesubstance than the thinner wall at the proximal end 129 and thuscollapse or contract in diameter first during expulsion of thesubstance. The expandable member 78 would then collapse progressivelyfrom the distal end 128 toward the proximal end 129 as the wall of theexpandable member 78 becomes thinner along its length in that direction.Because the thickness of the expandable member 78 preferablysubstantially uniformly increases from the proximal end 129 toward thedistal or closed end 128, the contractive force of the expandable member78 wall when expanded will increase substantially uniformly along thelength of the elongated expandable member 78 from the proximal port end129 to the distal or closed end 128. Thus, when the substance isexpelled into the subject, the expandable member 78 will progressivelycollapse in diameter as well as shrink in length, which collapse indiameter and shrinkage in length is preferably viewable by the user asdescribed above. The distal end 128 of the elongated expandable membermay allow for the connection of a movable indicator component 101 in theinjector 7 which will follow the shrinkage in length of the elongatedexpandable member 78. This indicator 101 is preferably viewable by theuser through the outer housing 74 and indicates the state of theinjector 7 and the progress of the injection. Alternatively, theexpandable member 78 is configured with a constant wall thickness andcould be prestressed in manufacturing to bias it to fill from theproximal end 129 to the distal end 128 and collapse or empty from thedistal end 128 to the proximal end 129 in a progressive manner aspreviously discussed.

Referring to FIGS. 36-39, the elongated expandable member 78 of theinjector 7 may be configured to have a section 130 of the expandablemember 7 adjacent to the proximal exit port end 130 that fills first andcollapses last during filling and expulsion of the substance from theinjector 7. In other words, during filling of the injector 7 by thetransfer apparatus, it is advantageous to have the most proximal exitport section 130 of the expandable member 79 to fill with injectablefirst. Additionally, during dispense of the substance from the injector7, it is advantageous to have the last remaining volume of substance tobe contained within the most proximal exit port section 130 theexpandable member 79. There are several advantages to the abovementionedconfiguration. The proximal end section 130 of the expandable member 78could have a thin wall that would cause it to remain inflated under alower pressure than the rest of the expandable member 78. This wouldassure that the section 130 of the expandable member 78 would remaininflated until all substance had been expelled from the rest of theexpandable member 78. As previously discussed, this section 130 may bedirectly coupled to an empty indicator to provide for full or emptyindication. Additionally, as previously mentioned, this section 130could be mechanically coupled to the empty indicator to allow for theautomatic withdrawal of the button 77 and cannula 82 upon completeexpulsion of the substance.

Referring to FIGS. 36-39, alternatively or in addition to varying thewall thickness 126 of the expandable member 78, an elongated internalmandrel or shaft 124 within the expandable member 78 may progressively(linearly or stepwise) decrease in cross-sectional size along the lengthof the expandable member 78 from proximal end (the exit port end) 129toward the distal end (closed end) 128 of the expandable member 78.Additionally, the manifold 121 which allows for attachment of theexpandable member 78 to the injector 7 may also be configured with alarge diameter section 130 at the proximal end 129 of the expandablemember 78. A large diameter section 130 of the mandrel 124 or manifold121 at the proximal end exit port 129 of the expandable member 78insures that the expandable member 78 will fill with substance in thisarea 129 first. In other words, the expandable member 78 is being heldat nearly a fill diameter at the proximal end exit port 129 by the largediameter section 130 of the mandrel 120 or manifold 121. As substancefirst starts to fill the expandable member 78, it reaches a filldiameter first in the large diameter section 130 then fillsprogressively along the length of the expandable member 78 from theproximal end 129 to the distal end 128 as previously discussed.

Referring to FIGS. 36-39, as previously discussed, during dispense ofsubstance from the expandable member 78, the diameter of the expandablemember 78 at its distal end continuously collapses in a progressivefashion (similar to deflating a long skinny balloon) from its distal 128to proximal end 129 until all of the fluid is expelled from theexpandable member 78. A large diameter section 130 of the mandrel 124 ormanifold 121 at the proximal end exit port 129 of the expandable member78 provides the same benefit (as previously described for filling)during dispense of the substance. This large diameter section 130insures that the last remaining substance in the expandable member 78will be contained and dispensed from this area 130. As previouslydiscussed, this section 130 may be directly coupled to an emptyindicator to provide for full or empty indication as well as for theautomatic withdrawal of the button 77 and cannula 82 upon completeexpulsion of the substance.

Referring to FIG. 21, the user attaches the injector 7 to their skin 99.There may be an adhesive on the bottom of the injector 7 that allows foradhesion to the skin 99 surface and hands-free operation. The adhesivemay extend past the outline of the injector to allow the user to firmlyadhere the tape to the skin. Alternatively, the user may hold theinjector 7 against the skin 99 for the duration of the injection.

Referring to FIGS. 21-23, the user removes the safety 100 and depressesthe button 77 on the injector 7 to start the injection. Once the button77 on the injector 7 is fully depressed, it is locked into place and thecannula will be fully inserted into the patient and the injector 7 willbegin dispensing the injectable drug. The injector 7 may alert the userthat injection of the drug has started. This alert could be in the formof visual indictors, audible sounds, mechanical movements or acombination. The time of the injection could be in a range of a fewseconds to several hours. The injector 7 may indicate to the user thatit is dispensing with the button 77 locked in the down position andindicator window 101 showing the injector 7 is less than full. Theinjector 7 preferably has a clear section 80 that allows the user toeasily determine the amount of drug remaining in the injector 7.

Referring to FIG. 24, the user will be alerted when the injection of thedrug is completed. This alert could be in the form of visual indicators,audible sounds, mechanical movements or a combination. The injector 7may indicate to the user that it is has completed dispensing with thebutton 77 moving to a locked-up position with tactile and audible soundsand indicator window 101 showing the injector is empty. At the end ofthe dispense, the cannula will automatically retract into a lockedposition within the injector 7.

Referring to FIG. 21, upon removal of the injector 7 from the skin 99, abandage 120 could release from the injector 7 and remain on the skinsurface 99. Upon removal from the skin 99, the injector 7 willpreferably be locked out, preventing non-destructive access to thecannula or reuse of the injector 7. The injector 7 may indicate to theuser that the full dose has been delivered. This indication could be inthe form of a visual indictor, audible sound, mechanical movement or acombination.

In accordance with further aspects of the present subject matter, whenadministering an injection with a syringe and cannula that is meant tobe infused under the skin, it is desirable to know if the cannula isproperly placed within the skin or improperly placed within a bloodvessel. It is common for a user performing an intradermal (ID),subcutaneous (SC) or intramuscular (IM) injection to aspirate thesyringe by pulling back on the plunger to create a pressure drop withinthe syringe to see if any visible blood comes up the cannula into thesyringe. If blood is visualized, this means the tip of the cannula is ina blood vessel. A number of injectable drugs meant for infusion underthe skin specifically indicate not to inject into a blood vessel. Bloodaspiration using a syringe and cannula is a common technique and can beperformed by anyone with adequate training. In some cases, anautoinjector may be used, and the autoinjector may comprise a mechanismfor determining whether the autoinjector is properly placed.

Referring to FIGS. 25-26, the injector 7 may have a cannula 85 with aside-opening (e.g., hole) 108 in operative engagement with the button 77slidable within a septum 109 advancing into the skin 99. The button 77may have a viewing window 160 on the button top 103 that is in fluidcommunication with the proximal end 161 of the cannula 85. The buttontop 103 may include a cavity 162 for blood 159 to accumulate and be seenthrough the button window 160 by a user. The cavity 162 may include acenter hole 163 that allows fluid communication with the proximal end161 of the cannula 85 via cannula lumen 165. The outer walls 164 of thecavity 162 are formed by the button top 103. Additionally, a portion ofthe outer walls 164 may include a hydrophobic filter 166. In thisconfiguration, the proximal end 161 of the cannula 85 is at atmosphericpressure. If fluid 14 or blood 159 travel up the internal lumen 165 ofthe cannula 85, it exits the proximal end 161 of the cannula 85 andfills the cavity 162. The air 167 in the cavity 162 is easily displacedthrough the hydrophobic filter 166 until all of the air 167 has beendisplaced from the cavity 162 and it is full of fluid 14 or blood 159.At this point, the flow of fluid 14 or blood 159 stops as the fluid 14or blood 159 cannot penetrate the hydrophobic filter 166 and can beeasily viewed through the window 160 of the button top 103 by the userthus providing a method for determining if the injector 7 cannula 85 isin a blood vessel 158.

Referring to FIG. 27, cannula insertion into tissue can be generallydivided into four stages. These include no contact (panel a), boundarydisplacement (panel b), tip insertion (panel c) and shaft insertion(panel d). During boundary displacement, the tissue boundary in thecontact area deflects under the influence of the load applied by thecannula tip, but the cannula tip does not penetrate the tissue. Theboundary of the skin follows the tip of the cannula up to a maximumboundary displacement point in the contact area as the cannula tipstarts to penetrate the skin. After the cannula tip penetrates the skin,the shaft is inserted into the tissue. Even after tip and shaftinsertion, the boundary of the skin surface in the contact area does notreturn to its original no contact state but remains displaced by adistance x. The amount of boundary displacement x is a function ofseveral parameters including but not limited to cannula diameter,cannula tip geometry, cannula shaft friction, cannula insertion speedand physical skin properties. Boundary displacement x of the skin in thecontact area is characterized in cannula-based injectors because iteffects how much of the cannula penetrates the skin and thereforereduces the actual cannula penetration depth by the amount of boundarydisplacement x. If the boundary displacement x could be intentionallyinduced by stretching or preloading such as pushing the skin out at thecontact site prior to cannula tip insertion, there would be noadditional boundary displacement by the cannula tip or shaft duringinsertion and the cannula tip depth could be predictably defined. Theadvantage of this intentional displacement is the amount of cannulapenetration into tissue would not be affected by variations in theboundary displacement x. Without intentionally inducing boundarydisplacement at the skin surface prior to cannula tip insertion, theactual cannula penetration depth into the skin is not specifically knownbecause some of the cannula length (depending on the abovementionedparameters) is outside the skin due to the naturally occurring boundarydisplacement x shown in FIG. 27. On the other hand, if the maximumboundary displacement could be induced at the contact site, the actualcannula penetration depth would not change with the variations in theabovementioned parameters including cannula diameter, cannula tipgeometry, cannula shaft friction, cannula insertion speed and physicalskin properties.

Referring to FIG. 28, the injector 7 may have a skin boundarydisplacement extension or structure, such as an underside surface 76that includes an extension 138 at or around the dispense port 82 or aspart of the dispense port 82. The extension extends substantially normalto plane of the tissue at the point of cannula insertion. When theinjector 7 is attached to the skin 99, the extension 138 will protrudeagainst the skin 99 surface resulting in displacement or compression ofthe skin 99 in this contact area 139. The compression of the skin helpsto reduce or eliminate “tenting” of the tissue surface upon cannulainsertion. In other words, by “pre-loading” the tissue by compressingit, the extension 138 serves to eliminate further tissue defection ortenting, or results in more reproducible and lesser amount of skinsurface deflection or tenting. During actuation of the button 77 from apre-fire state to first position, the cannula 85 advances out of theinjector 7 through the dispense port 82 and/or extension 138 into theskin 99 to start the dispense of drug. For the reasons described above,as the cannula 85 advances out of the injector 7, the tip of the cannula107 does not produce additional boundary displacement 141 (alreadyintentionally induced by the extension 138) in the skin 99 at thecontact area 139. Thus the actual cannula penetration depth 140 into theskin 99 is better characterized and controlled. Also, the extension,through which the cannula passes, compresses the tissue immediatelyaround the cannula, which has several advantages. During the injection,the compression of the tissue by the extension 138 in the contact area139 increases the local density of tissue thus creating ahigher-pressure zone compared to the surrounding adjacent tissue 99. Asinjectable enters the skin 99, the fluid will migrate from thishigh-pressure zone 139 to lower pressures areas in the skin 99 whichhelps to prevent injected fluid or drug from flowing or migrating intothe immediate area around the cannula/skin puncture site and acts toreduce or minimize fluid leakage (backflow) and/or bleeding from thepuncture site. This higher-pressure zone also effectively provides thebenefit of a much longer injection cannula. For example, in anultrasound evaluation comparing the subcutaneous deposition depth of a10 mL fluid bolus (saline) using the injector 7 with a 5 mm needle depthand an off-the-shelf infusion pump (Freedom 60, RMS) with a butterflyneedle extension set (9 mm needle depth), results show that thesubcutaneous depth of the 10 mL bolus, post injection was equivalentbetween the injector 7 with a 5 mm needle length and the pump with a 9mm needle length. In all results, bolus position is characterized bydistance (Zd) from the skin surface to top edge of bolus. FIG. 47 showsthe top edge of the 10 mL subcutaneous bolus using the pump with 9 mmcannula length. The Zd distance is measured at 0.44 cm. FIG. 48 showsthe top edge of the 10 mL subcutaneous bolus using the injector 7 with a5 mm cannula length. The Zd distance is measured at 0.42 cm. Thus, asimilar depth of the bolus is provided with a cannula depth (5 mm) andthe tissue displacement structure that is more than 40% shorter than theother tested cannula (9 mm) without a tissue displacement structure.

Another advantage of the extension 138 is compression of the tissue inthe contact area 139 after the injection has completed. In thepost-fired state, the button 77 has popped up alerting the user that theinjector 7 has completed. The cannula 85 is fully retracted out of thepuncture hole in the skin 99. The dwell time between when the injector 7has completed dispense and is removed by the user can be several minutesor more, depending on the environment in which the user is in at thetime of completion. For the same reasons described earlier, thecompression of the tissue by the extension 138 in the contact area 139increases the local density of tissue thus creating a higher-pressurezone compared to the surrounding adjacent tissue 99. Similar to how anurse may apply pressure to an injection site with their thumb afterinjection, this pressure helps close the puncture hole and preventsinjected fluid or drug from flowing back up the injection site and actsto reduce or minimize fluid leakage and/or bleeding from the puncturesite.

Referring to FIG. 29, there are two interfaces related to adhering theinjector 7 to the skin 99. The first is the adhesive/device interface173 and the second is the adhesive/skin interface 174.

Referring to FIG. 30, the adhesive 88 could be configured on theinjector 7 with at least two zones. The first zone 175 may include apermanent bond using mechanical or chemical means between the adhesive88 and the injector 7 and preferably be positioned within the perimeterof the injector 7. The second zone 176 may be configured to bedetachable or unattached from the injector 7 and preferably be adjacentand on the outside (e.g., radially outward) of zone 1.

Referring to FIG. 31, if the adhesive 88 were completely attached to thebottom 76 of the device 7, during a tissue bulge 177 event the adhesive88 at the adhesive/skin interface 174 would start to peel from the skin99 because this interface 174 is weaker than the adhesive/deviceinterface 173. This is demonstrated on a bulging surface in FIG. 31.This may result in the injector 7 becoming dislodged from the skinsurface 99 and falling off the patient.

Referring to FIGS. 30 and 32, instead of permanently attaching theadhesive 88 completely to the bottom 76 of the injector 7 as shown inFIG. 31, the adhesive 88 could be configured on the injector 7 with theabovementioned zones 175, 176. During a tissue bulge event 177 in thisconfiguration, the adhesive 88 in zone two 176 would detach from theinjector 7 and be firmly attached to the skin 99 surface at theadhesive/skin interface 174. This would allow for transfer of the peeledge 178 from the adhesive skin interface 174 to the adhesive/deviceinterface 173 effectively creating a strain relief at the adhesive/skininterface. The adhesive/device interface 173 may be designed to be muchstronger and prevent injector 7 separation from the skin surface 99.

When performing self-injections with automatic injectors, protecting theuser from accidental cannula sticks is a beneficial requirement for thedevice. Typically, the cannula is retracted within the device before andafter use, preventing the user from accessing the cannula. However,during the injection, the cannula can be extended outside of the device.In some instances, the automatic injector comprises a skin dislodgementsensor to automatically retract a cannula if the device becomesdislodged from the skin during the injection.

Referring to FIG. 33-35, a skin dislodgement sensor 179 may be inoperative engagement with a flexible latch 181 of the button 77 andslidable within the lower housing 180 of the injector 7. Referring toFIG. 34, when the injector 7 is attached to the skin surface 99, theskin dislodgement sensor 179 is forced into a first or up position 182inside the injector 7. When the button 77 is actuated to a fired stateor second position or dispense position (exposing the cannula 85), theflexible latch 181 is forced into a lock position 187 by the skindislodgement sensor 179 under the latch board 183. The latch board 183holds the button 77 at the latch board surface 184 on the button 77 downin the fired state or dispense position until the end of dispense. Atthe end of dispense, the latch board 183 translates away from the latchboard surface 184 on the button 77, allowing the button 77 and cannula85 to retract to a post fire position where the cannula 85 is containedwithin the injector 7. Referring to FIG. 35, in the event that theinjector 7 becomes dislodged from the skin surface 99 during injection,the skin dislodgement sensor 179 extends to a second or down position185 out of the injector 7. This allows the flexible latch 181 to springback to an unlocked position and disengage from the latch board 183.This allows the button 77 and cannula 85 to retract to a post fireposition where the cannula 85 is contained within the injector 7.

When performing self-injections with a syringe and cannula, users mayhave the need to temporarily stop or pause the injection due to acutepain or irritation at the injection site. This pause in flow ofinjectable into the injection site, accomplished by removing pressure onthe plunger rod of the syringe, helps to reduce the pain at theinjection site by allowing the injectable fluid bolus more time todiffuse into the surrounding tissue and thus reducing the local pressureand associated pain and irritation. In some instances, the injectorcomprises a mechanism for pausing the injection, e.g., automatically ormanually.

Referring to FIGS. 36-37, upon actuation of the button 77, the cannula85 and button 77 travel to a first position or depth as shown in FIG.36. In this first position or depth, the side-hole 108 is covered by theseptum 109 and therefore the internal lumen 165 of the cannula 85 is notin communication with the fluid channel 86 of the dispense port 82. Thebutton 77 may be intentionally held in this first position or depth toprevent flow of injectable 14 from the fluid channel 86 into theside-hole 108 of the cannula 85 and into the skin 99. As shown in FIG.37, when the button 77 is released, the cannula 85 and button 77 returnto a second position or dispense position where the side-hole 108 isexposed to the fluid channel 86 allowing the flow of injectable 14 fromthe fluid channel 86 into the side-hole 108 of the cannula 85 and intothe skin 99 until the end of the injection. This action of pushing thebutton 77 to the first position or depth may be performed as many timesa necessary during the entire injection.

Referring to FIGS. 38-39, the button 77 actuation force 186 is thetransition load applied to the button 77 required to start displacementof the button 77 and cannula 85 from a pre-fire position to a firedstate or dispense position. Until this transition load is met, the force186 applied to the button 77 is transferred directly to the injector 7.Specifically, this load 186 may be transferred to adhesive skininterface 174 and/or the adhesive device interface 173 resulting inbetter securement of the injector 7 to the skin surface 99 prior toactuation of the injector 7.

Referring to FIGS. 40-41, the arcuate expandable member 78 is positionedand/or will preferably expand in length in an arc shape. In theillustrated embodiment, the arc shape is induced by providing a lessresilient area for example a thicker or relatively heavy wall thicknesszone 126 which will result in less deflection of the expandable memberin that zone and result in formation of an expanded arc shape. Thisheavy wall thickness zone 126 may be configured in any shape that willallow for the arc shape in the expandable member 78 during expansion. Apreferred configuration for the heavy wall thickness zone 126 is tominimize its thickness or attachment 150 in the circumferentialdirection on the expandable member 78 wall and maximize the radialthickness or projection 151 away from the expandable member 78. Thisserves to urge the expandable member 78 to expand in an arc shape butalso maximizes the amount of material along the circumference that isunaffected by the heavy wall thickness zone 126 for expansion.Additional features including but not limited to a T-shape may beconfigured to the end of the radial projection 152 to help urge theexpandable member 78 into an arc shape.

Referring to FIG. 42, a safety, such as a safety pin or safety sleeve100 may be configured to allow for removal from the injector 7 in anydirection to release the injector 7 to be ready to fire (inject).

Referring to FIG. 43, the injector 7 includes a cannula 85 with aside-hole 108 that allows for fluid communication between the fluidchannel 86 and the skin 99 once the button 77 is fully depressed in theinjector 7. This starts dispensing of the injectable 14. The innerdiameter 165 of the cannula 85 is significant in controlling the rate ofdispense from the injector 7. Referencing the Hagen-Poiseuille equationfor fluid flowing in a pipe, the flow rate through a pipe is directlyproportional to the radius of the pipe to the fourth power. Thus, smallvariations in the inner diameter 165 of the cannula 85 result in largevariations in flow through the cannula 85, especially as the innerdiameter 165 gets smaller. The cannula 85 in the injector 7 may rangefrom 21G to 34G (Stubs Iron Wire Gauge System) in various wall thicknessconfigurations. This range corresponds to an inner diameter 165 range of0.021″ to 0.003″, recognizing that there is manufacturing variation ortolerance with the cannula inner diameter 165 in any given cannula size.This is based on cannula size and can have an inner diameter variationas much as ±0.00075″. To limit the range of the inner diameter 165within any given cannula size and resulting variation in flow, thecannula 85 may be modified prior to assembly into the injector 7. Thismodification could include crimping, flattening or rolling the cannulato a new, prescribed effective inner diameter 165 over a portion of thelength of the cannula 85 from a circular shape to a non-circular shape.This has the advantage of allowing for specific delivery rate controlfrom the injector 7.

Radiofrequency Compliance Monitoring

In some instances, the injector comprises a mechanism to alert thesubject, the prescriber, the healthcare provider or another third-partyparticipant when non-compliance or non-adherence is occurring.

In accordance with further aspects of the present subject matter, whenadministering an injection with an automatic injector, it is desirableto know when the prescription for the injector was initially filled orrefilled as well as whether the injector was used properly and on time.While many prescription drugs are tracked at the time they are filled bythe patient using specialized labeling, there are limited options toconfirm if the patient actually took the medication. As more drugs arebeing presented in injectors, the ability to automatically trackprescription initiation currently has limited usage. Further, theability to automatically track whether the injector was used properlydoes not exist.

As described herein, automatic tracking both for adherence andcompliance can be accomplished wirelessly using RF (radio frequency)techniques installed within or in cooperative association the transferand/or injectors described herein. Current technology allows for the useof radio-frequency identification (RFID) to transfer data, for thepurposes of automatically identifying and tracking tags or microcircuitchips attached to objects. As used herein, RF or RFID or RF tags or RFchips are used comprehensively and interchangeably and are intended toinclude wireless electronic tags or chips for transmittingdata/information using any suitable wireless communication protocol ortechnology, such as Bluetooth or any other wireless technology (e.g.,wireless LAN, wireless PAN, or other wireless technologies described inthe Institute of Electrical and Electronics Engineers (IEEE) 802standards).

RF tags or chips may be active or passive. While both types use RFenergy communicate between a tag or transponder and a reader, the methodof powering the tags is different. Active RFID uses an internal powersource (such as a battery) within or associated with the tag tocontinuously power the tag and its RF communication circuitry, whereaspassive RFID relies on RF energy transferred from the reader to the tagto power the tag. In the present subject matter, the injector or thetransfer package may include an RFID tag, may optionally include a powersource for the tag and be read or received by an external reader. In oneembodiment, the RF tag or chip is removably associated with the injectorsuch that it can be physically removed from the injector when theinjector is used. This allows for the subsequent disposal of theinjector free of the limitations or restrictions that might apply if thetag or chip remained as part of the injector after its use.

Referring to FIGS. 44-45, the injector 210 may include an electronic RFtag or chip 211 to monitor the status of the injector 210. For example,the RF tag 211 may broadcast to an external reader 212 (if active) orpresent (if passive, read by an external reader 212) information orstatus—such as “the injector 210 has been prescribed,” “the injector 210has been removed from its packaging,” and “the injector 210 has beenactuated” and/or “the injector 210 has completed its dose.” The RF tagreader could also be associated with or in communication with an on-siteor off-site data collection facility, such as by wireless or hardwiredconnection to allow recordation and compilation of information regardingcompliance.

Referring to FIGS. 44-45, an RF tag 211 may be used to monitor whetherthe injector 210 has been activated or has initiated or completed itsdose. The injector 210 may include an active or passive radio frequency(RF) tag or chip 211 at any suitable location. As shown below, when usedinternally of the injector, the RF tag or chip 211 may be attached tothe button 213 and in slide-able communication with the spring tabs 214during the first and second positions of the button 213. While the RFtag 211 is in slide-able communication with the spring tabs 214, the RFtag 211 may broadcast (if active) or present (if passive, read by anexternal reader 212) a first state to include an unused status. In theevent the injector 210 is activated, the button 213 is depressed to thedispense position. At the end of the dispense period, the button 213 isunlocked from the second depth or dispense position (shown in FIG. 45)to move up to a final position or post fire position. At this post-fireposition, the RF tag 211 may no longer be in contact with the springtabs 214, thus allowing for a change in state (second state) of the RFtag 211. In this second state, the RF tag 211 may broadcast (if active)or present (if passive, read by an external reader 212) a second stateto include a used status. Alternatively the RF tag 211 may be deformedor altered in such a way upon use of the injector that, uponinterrogation, the RF tag 211 presents a ‘used’ signature. For instance,if the RF tag consists of two coils joined by a conductor, the initialsignature of the tag 211 would be the ‘dual coil’ signature. Once thetag 211 has been used, if the conductor joining the two coils is broken,then the two independent coils produce a different signature.

Location of the RF tab or chip outside of the injector may be desiredfor regulatory and/or disposability reasons. For example, the RF tag orchip 211 also may be associated with the transfer device or with anotherpart of the system, such as for example, safety sleeve or pull tab 100(see FIG. 42), to activate the tag or chip at a selected point or pointsin the operation of the transfer device and/or injector. An active RFtag or chip could, for example, be located on the safety sleeve andconfigured so that removal of the safety sleeve to start the injectionprocess closes a contact between a long shelf-life battery and the tagor chip transmitter.

Referring to FIGS. 52-55, the RF chip or tag 211 within the injector 210may have two states, a standby or off state and an active, ortransmitting, state. With reference to FIGS. 52 and 54, the state may bechanged by making or breaking a contact between a battery 262 and acontact 263. As illustrated in FIG. 54, this may be achieved, forexample, by configuring the safety release or pull tab 100 to preventelectrical contact between the battery 262 and the contact 263 byspatial separation when the pull tab 100 is in position on the injector210. Upon removal of the pull tab 100, as illustrated in FIG. 55, thebattery 262 and contact 263 come together to contact one another andmake electrical contact. As a result, the RF tag begins to function.Further, different actions associated with the use of the transferand/or injector could be employed to make or break contact. For example,a previously inactive RF tag or chip could be activated by closing acontact between a battery and the chip or tag transmitter when oneaction is taken, such as when a vial is inserted into the transferdevice, and deactivated by another action, such as by breaking suchcontact after use of injector.

The RF tag or chip 211 may transmit or communicate data associated withthe transfer or injector—in addition to use information. For example,the tag or chip may be configured, with memory storage capacity, totransmit the type of injector, lot number, fluid quantity administered,drug identification and other relevant information. FIG. 46diagrammatically illustrates one system that may be employed with thepresent subject matter. As shown there, the RF tag or chip 250 may be ofthe active type, and when activated actively transmits the pertinentinformation to a local Patient Module 252 located within the vicinity ofthe patient and injector. For example, the Patient Module could be awall-mounted or desktop device located in the patient's home forreceiving the monitoring information transmitted by the RF tag or chipassociated with the injector and/or transfer device. The Patient Modulecould also be a cellular telephone or the like.

The Patient Module could include a memory that maintains data such aspatient identification and related information. The Patient Module, inturn, communicates in an appropriate manner, such WIFI, cellularcommunication, telephone, hard wire link or other, with a Data Manager254, which could be any appropriate data network or Cloud storagearrangement for receiving and/or storing data received from the PatientModule indicating injector status and/or usage in association with theparticular identifying patient information. The Data Manager would beaccessible by medical personnel responsible for the monitoring of thepatient's use of the injector and patient compliance with any prescribedinjection regimen. The Data Manager could also be configured toautomatically relay patient compliance information to the appropriatemedical personnel, such as a particular physician or clinic 256.

Other aspects of a compliance monitoring apparatus, system and methodand use with an injector such as described herein are shown in FIGS.49-58. As illustrated there, the system may include a wireless, e.g.,Bluetooth, source, such as a battery powered sending unit such as amicrochip, indicated at 262 in FIG. 59. The sending unit may be mountedin any suitable location, and can be associated with or attached to apart of the injector (an/or transfer device) in a manner so that it canbe detached from the injector or transfer device at the time ofdisposal—allowing most of the injector or transfer device structure tobe recycled, as electronic circuitry and electronic chips are typicallynot similarly recyclable.

In some embodiments, a contactor ring is provided in the top of the ofthe injector housing and is prevented from making contact with sensingleads (which are attached to the injector button) when a safety strip isinstalled. When the safety strip is removed, the contactor ring of thehousing makes contact with the sensing leads of the button. Differentsequences of the injection process may then be tracked based on theconnection status between the contactor ring and the sensing leads (i.e.position of the contactor ring with respect to the sensing leads).Infrared sensors may also be embedded in the injector to optically trackdelivery progress, such as by, for example, monitoring of the positionof, or amount of injectable fluid in, expandable member of the injector.

Referring to FIGS. 52 and 53, an embodiment of the RF tag or chip 211includes the following components: Battery 262, Contact 263, BluetoothModule with Microcontroller/Microprocessor 265, Button Sensors 267 andAntenna 269. The battery 262 provides for the stored energy to power thesystem. This can be a coin-cell battery or equivalent in the voltagerange of 1.5-3V with a power output of 5-100 mAh. As explainedpreviously, the contact 263 provides the electrical connection betweenthe battery 262 and the RF tag or chip 211. The contact 263 isconfigured to interact with the pull tab 100 to allow for no electricalcontact until the time of use when the user removes the pull tab 100.The Bluetooth module 265 has an integratedmicrocontroller/microprocessor. An example of a suitable Bluetoothmodule is Dialog Semiconductor Part number DA14580-01UNA. In alternativeembodiments, the Bluetooth module may be separate from themicrocontroller/microprocessor.

The button position sensing system in an embodiment of the device isillustrated in FIGS. 56 and 57. The sensing system can use an infraredemitter and receiver sensor combination 267. The RF chip 211 is mountedto an underside surface of the device button 177 with the sensors 267facing downwards. A reflecting member 112 is mounted to the bottom ofthe injector in a fixed fashion. When the device button is actuated soas to move from the up, raised or extended position illustrated in FIG.56 to the down, lowered or retracted positioned illustrated in FIG. 57,the sensors 267 detect the decrease in distance from reflecting member112. Conversely, when the button is released after delivery of the drugso that it moves from the position of FIG. 57 to the position of FIG.56, the sensors 267 detect the increase in distance from reflectingmember 112. The sensors 267 transmit this button position information tothe microcontroller/microprocessor module 265.

The processing performed by the microcontroller/microprocessor module265 in an embodiment of the device is presented in FIG. 58. A starttimer, indicated at block 302, is initiated when themicrocontroller/microprocessor is powered up, such as by removal of thesafety tab 100 as described with reference to FIGS. 54 and 55 above. Themode or status of the device is then set to “Ready to Fire” (i.e. readyto dispense) as indicated by block 304 and a Bluetooth packet indicatingthis mode for the device is transmitted to a Bluetooth-enabled remotereader or receiver (such as 212 of FIGS. 44-45), which may be, asexamples only, a smart phone or a computer system. The mode is displayedon the remote receiver to a user.

The processing of blocks 308 a can then performed to conserve thebattery life of the device and compute timing of the device.

The microcontroller/microprocessor then checks the position of thedevice button (177 in FIGS. 56 and 57), as indicated by block 312 using,for example, IR sensors as described above with reference to FIGS. 56and 57. As indicated at 314, the above processing is repeated if thedevice button has not been pressed into the down position. If the devicebutton has been pressed down, a start time for the delivery of theinjectable is recorded, as indicated by block 316, and the device modeis set to “Dispensing”, as indicated by block 318. This mode istransmitted to the remote receiver, as indicated by block 322, where itis displayed to the user.

The processing of blocks 308 b is then performed to conserve the batterylife of the device and compute timing of the device by intermittently oralternately placing the processor in a low energy sleep mode and thenawakening the processor at one second (or other suitable time)intervals.

The microcontroller/microprocessor then checks the position of thedevice button, as indicated by block 324. As indicated at 326, the aboveprocessing beginning with block 322 is repeated if the device button hasnot returned to the raised or up position. If the device button hasmoved into the up position, an end time for the delivery of theinjectable is recorded, as indicated by block 332, and the device modeis set to “Completed”, as indicated by block 334. This mode istransmitted to the remote receiver, as indicated by block 336, where itis displayed to the user.

The processing of blocks 308 c is then performed to conserve the batterylife of the device and compute timing of the device, after which the“Completed” status of the device is again transmitted to the remotereceiver (block 336).

Embodiments of the disclosure may provide ‘smart’ connected devices thatenable patients to self-administer high volume/viscosity drugs, enablingand promoting patient freedom and mobility. Embodiments may provide theuser with a safe, simple, and discreet drug delivery experience.

Embodiments of the disclosure may provide a smart device system toprovide three pieces of information about the operation of the drugdelivery system: 1) When the device is powered on, 2) when the devicehas started delivery and 3) when the delivery has been completed. Theuser interaction in some embodiments can comprise opening the mobileapplication on their device, as described elsewhere herein, and thesmart device will do the rest without requiring additional operationsfrom the subject or user.

Embodiments of the disclosure may provide advantages such as: smallboard footprint—the entire electronics package fits inside the existingbutton and is less than ⅜-inch (9.5 mm) in diameter. This allows foreasy removal of the electronics (button) for electronic disposal andrecyclability.

Embodiments of the disclosure may include smart device technology in thetransfer device. For example, the transfer device may includeelectronics to track the usage of the transfer device. The electronicsin the transfer device could communicate directly with an externalreceiving device and/or to the electronics in the patch/injector.Transducers/sensors within the transfer device electronics could provideinformation including but not limited to environmental conditions,opening of the outer box or packaging, removal of the transfer devicefrom the outer packaging, orientation of the transfer device (tiltsensing), the position of the device (e.g., using a global positioningsystem, or GPS) whether the transfer device is located on a flatsurface, vial insertion, plunger release (venting), and/or removal ofthe injector from the transfer device. Electronics in the transferdevice could determine if the correct vial has been inserted basedelectronics within the vial or reading of bar codes/QRG codes.Activation of the electronics could occur when the outer box orpackaging is opened, when the transfer device is removed. Additionalelectronics could be added to vibrate or make a sound if the device isnot placed on a table or at an angle. The electronics in conjunctionwith an external receiver could provide voice commands to aid the userin using the device or provide instruction if something is doneincorrectly.

In certain embodiments of the disclosure, the injector may utilizeBluetooth communications to provide data to the user. Furthermore,embodiments may integrate Bluetooth Low Energy (BLE) into the device.BLE can be designed for low power, low cost applications that requirelower data throughput rates than traditional Bluetooth connections suchas audio streaming or hands-free phone connections.

There are two major types of connections defined in the Bluetoothstandard: Standard (bonded) mode and Broadcast (also known as “beacon”)mode. In standard or bonded connections, a host (smartphone withinstalled app) creates a saved connection with a peripheral (i.e., asmart device). In this scenario, through the pairing process, both thehost and the peripheral share data to create a permanent connection thatallows sharing between only one host and one peripheral. This method hasthe advantage of a secure connection allowing the exchange of encryptedinformation that cannot be decoded without the encryption key.

In broadcast mode (also called a “beacon”), the peripheral sends outdata at regular intervals that can be read by any nearby host. In thisscenario, the peripheral only broadcasts data; data is never received.There are several advantages to this mode, e.g., reduced powerconsumption. In some instances, further power savings can be achievedthrough lower power ‘sleep’ mode, waking up only when new data needs tobe broadcast;

Additionally, as the peripheral can be configured to be a transmit-onlydevice, enhanced security is provided as the hardware cannot be‘hijacked’ or loaded with malicious software. This reduces or eliminatesthe risk of unauthorized remote control of the device. The software isloaded onto the device in the factory, preventing unauthorizedalteration once deployed.

In some instances, installation of an application, as describedelsewhere herein, may be used for securing data privacy. For instance,without proper application installation, the data can simply consist ofan unusable list of binary numbers, lacking any text or other readableidentifiers. Because of this, the lack of an encrypted connection doesnot expose any sensitive user information. The data may also excludepatient information—such as names or identification numbers—which couldbe associated with a specific individual (thereby following HIPAACompliance).

An important attribute of the connected healthcare implementation withinembodiments of the disclosure may be that it does not affect theessential performance functions of the drug delivery device. In someembodiments, this feature of the device only reports the status of thedevice and in no way alters the function of the drug delivery device.Even in the event of a critical failure of the Bluetooth components,such as the battery, some embodiments of the device will complete thedelivery of the drug and provide the user with visual feedback as to thedevice status.

Utilizing the Bluetooth Low Energy broadcast mode and through anelectronic chip in the button of the device, some embodiments of thedisclosure can deliver real-time device performance information in asmall, low cost, convenient package.

Injector with Patch

In an aspect, the present disclosure provides a system for measuring aplurality of health or physiological parameters from a subject. Thesystem may comprise a patch comprising a first housing having aplurality of sensors configured to (i) measure the plurality of healthor physiological parameters from the subject when the patch is securedto a body of the subject, and (ii) provide one or more outputscorresponding to the plurality of health or physiological parametersfrom the subject. The first housing may comprise an opening. The systemmay also include an injector having a second housing comprising acannula in fluid communication with a fluid flow path. The secondhousing may be coupled to the first housing such that the cannula isdirected through the opening and in contact with a body of the subjectwhen the patch is secured to the body. The injector may be configured to(i) direct a substance from a reservoir to the fluid flow path in fluidcommunication with the reservoir, and (ii) direct the substance from thefluid flow path into the subject through the cannula.

The cannula may be configured to extend towards or retract away from thebody of the subject. In some examples, the cannula extends towards thebody of the subject to deliver the substance into the body of thesubject (e.g., across a skin of the subject). Subsequent to delivery ofthe substance, the cannula may retract away from the body of thesubject. The cannula may be connected to the reservoir via a fluid flowpath. The cannula may extend to and/or retract from the body using avariety of mechanisms, e.g., mechanical, electrical, etc. The means forcannula extension and retraction may comprise pumps, springs, gears,diaphragms, screws, or other means to move the cannula, or variations orcombinations thereof.

The injector may be detachable from the patch. The patch may comprise afirst housing, and the injector may comprise a second housing, and thefirst and second housing may be removably coupled. In one example, thefirst housing of the patch may be mechanically coupled to the secondhousing of the injector using one or more fastening mechanisms. In somecases, the first housing and/or the second housing may comprise magnetsthat allow for removable coupling, as described elsewhere herein. Inanother example, the first housing and the second housing may beadhered, e.g., using adhesive tape. The adhesive force of the firsthousing and the second housing may be modulated based on desiredproperties. For example, it may be desirable to maintain the patch onthe body of the subject while removing the injector. In such examples,an adhesive layer can be added to the patch that may facilitate securingof the patch to the body of the subject. This body-adhering adhesivelayer may have a stronger adhesive force between the patch and the bodyof the subject than the adhesive force between the patch and injector.In yet another example, the first housing and the second housing may bemechanically coupled, e.g., using interlocking geometries of the firsthousing and the second housing. For example, the first housing maycomprise threads (e.g., screw threads, internal threads, etc.) and thesecond housing may comprise complementary threads that may engage withthe threads of the first housing. In conjunction or alternatively, thefirst housing and/or the second housing may comprise snap-fit joints(e.g., cantilever snap fits, annular snap fits, etc.) that allow forinterlocking of the first housing to the second housing. Alternatively,or in conjunction, the first housing and/or the second housing maycomprise components that allow for interference fits, force fits, shrinkfits, location fits, etc. Other examples of fastening mechanisms mayinclude, in non-limiting examples, form-fitting pairs, hooks and loops,latches, threads, screws, staples, clips, clamps, prongs, rings, brads,rubber bands, rivets, grommets, pins, ties, snaps, Velcro, adhesives(e.g., glue), tapes, vacuum, seals, a combination thereof, or any othertypes of fastening mechanisms. Alternatively, the injector may bepermanently attached to the patch. For example, the first housing may beconnected to the second housing or may be monolithically built into thesecond housing, or vice-versa.

In some instances, the patch and the injector can be fastened to eachother via complementary fastening units. For example, the patch and theinjector, or the housing of the patch and the housing of the injector,can complete a form-fitting pair. The patch can comprise a form-fittingmale component and the injector can comprise a form-fitting femalecomponent, or vice versa. In some instances, an outer diameter of aprotrusion-type fastening unit of the patch can be substantially equalto an inner diameter of a depression-type fastening unit of theinjector, or vice versa, to form an interference fit. Alternatively, orin addition, the patch and the injector can comprise other types ofcomplementary units or structures (e.g., hook and loop, latches,snap-ons, buttons, nuts and bolts, magnets, etc.) that can be fastenedtogether. Alternatively, or in addition, the patch and the injector canbe fastened using other fastening mechanisms, such as but not limited tostaples, clips, clamps, prongs, rings, brads, rubber bands, rivets,grommets, pins, ties, snaps, Velcro, adhesives (e.g., glue), magnets ormagnetic fields, tapes, a combination thereof, or any other types offastening mechanisms.

In some instances, the patch and the injector can be fastened to eachother via an intermediary structure. In some instances, the intermediarystructure may be fastened to one or both of the patch and the injectorthrough one or more of any of the fastening mechanisms described herein.The intermediary structure may comprise a solid material, semi-solidmaterial, liquid material (e.g., a resin that is configured tosolidify), or multiple material types. In some instances, theintermediary structure may undergo phase transitions (e.g., liquid tosolid for an adhesive). For example, the intermediary structure maycomprise a fluid adhesive that solidifies to achieve the fastening. Insome instances, the intermediary structure may be capable oftransforming from a first phase to a second phase, such as from liquidto solid or from solid to liquid, upon application of a stimulus (e.g.,thermal change, pH change, pressure change, applied force, etc.) toachieve fastening or unfastening (or both). In some instances, the patchand/or the injector may comprise the intermediary structure. Forexample, the intermediary structure may be integral to the patch and/orthe injector.

The fastening between the patch and the injector can be temporary, suchas to allow for subsequent fastening and unfastening of the patch andinjector without damage (e.g., plastic deformation, shear deformation,wear, compression deformation, etc.) to the patch or injector.Alternatively, the fastening can be permanent, such as to allow forsubsequent unfastening of the two patches from the injector. In somecases, it may be desirable to deform either the patch or injector, andeither the patch or injector may temporarily or permanently be deformed(e.g., stretched, compressed, etc.) and/or disfigured (e.g., bent,wrinkled, folded, creased, etc.) or otherwise manipulated when fastenedto the injector or patch. The opening may comprise a pierce-ablemembrane. The pierce-able membrane may be pierced by the cannula togenerate the opening. The pierce-able membrane may be formed of apolymeric material, or the pierce-able membrane may be formed ofmultiple polymeric materials. The polymeric materials may be naturallyoccurring or may be synthetic. Non-limiting examples of polymericmaterials include poly vinyl chloride (PVC), polyethylene, polyurethane.In some cases, the pierce-able membrane may further comprise an adhesivelayer (e.g., acrylate, methacrylate, epoxy diacrylate, or other vinylresins, etc.). In some cases, the pierce-able membrane may comprise aself-healing polymer or elastomeric material, such that the opening thatis introduced by the cannula may be closed, e.g., after cannularetraction. In such cases, the pierce-able membrane may include anopening, e.g., hole or slit that is configured to form a seal in theabsence of the cannula directed through the opening. In some examples,the pierce-able membrane may include an opening that is not configuredto seal in the absence of the cannula directed through the opening.Alternatively, the opening may not comprise a pierce-able membrane andthe opening may be configured to be in direct line of sight with thebody of the subject. The opening may be any suitable shape, e.g., aslit, triangular, square, rectangular, rhombus, pentagonal, hexagonal,heptagonal, octagonal, polygonal, ellipsoid, annular, circular, etc. Insome cases, the pierce-able membrane comprises an absorbent material,e.g., cotton, rayon, nylon, a polymer, a polymer blend, etc. In suchcases, the pierceable membrane may be used as a bandage and can collectbodily fluids (e.g., sweat, blood, etc.) from the body of the subject.In some instances, the pierceable membrane may comprise anoxygen-permeable material, which may allow for exposure of the body ofthe subject, or portion thereof, to the ambient air. In some cases, thepierceable membrane may comprise a medicament (e.g., analgesic ormedicament for treating pain).

The reservoir may be secured to the injector. In some cases, thereservoir is removable from the injector. For example, the reservoir maycomprise a container or be a part of a container. The reservoircontainer may be removably coupled to the injector (e.g., attach anddetach from the housing of the injector). The housing may containfasteners to secure the reservoir. Alternatively, the geometry of theinjector may be designed to fit the reservoir or reservoir container. Inother cases, the reservoir may be part of the injector (i.e., notremovable). In one example, a medicament reservoir may be provided inthe housing and may be in fluid communication with the injectioncannula. For example, the injection cannula may be moveable within thehousing between a pre-dispense position and a dispense position in fluidcommunication with the reservoir. The reservoir may be configured tocontain a formulation having the substance.

The substance may comprise a medicament. The medicament may be asolution or a mixture. The medicament may be used for treating diseasesin a range of therapeutics areas including but not limited tocardiovascular, musculoskeletal, gastrointestinal, dermatology,immunology, ophthalmology, hematology, neuroscience, oncology,endocrinology/metabolic and respiratory. The medicament may be used totreat discomfort or pain of the subject. For instance, the medicamentmay comprise an analgesic, non-steroidal inflammatory drug (NSAID), orother pain-reducing, pain-alleviating, or other pain managementsubstance.

The housing of the patch and/or the housing of the injector may compriseone or more polymer or plastic materials. Non-limiting examples ofpolymers include polyamides, polycarbonate, polyester, polyethylene,polypropylene, polystyrene, polyurethane, polyvinyl chloride,polyvinylidene chloride, acrylonitrile butadiene styrene, polymethylmethacrylate, polytetrafluoroethylene, polyimide, polylactic acid,phenolics, polyetheretherketone, or derivatives thereof (e.g., highlycross-linked, high density, etc.). The housing of the patch and/or thehousing of the injector may comprise a single polymer type (e.g., ahomopolymer) or more than one polymer type (e.g., a copolymer) andcomprise a random or arranged organization of monomers. For example, apolymer may be a block polymer, an alternating copolymer, periodiccopolymer, statistical copolymer, stereoblock copolymer, gradientcopolymers, branched copolymers, graft copolymers, etc.

A sensor and/or transducer may comprise one or more sensors ortransducers that allows for measuring or monitoring a health orphysiological parameter or a plurality of health or physiologicalparameters or allow for indication of device function to the subject.Alternatively or in conjunction, one or more sensors may allow formeasuring of patch or injector parameters. Non-limiting examples ofpatch or injector parameters include determination of whether the patchis secured (e.g., to a body of the subject), whether the patch orinjector is in communication with the communication interface, whetherthe cannula is in fluid communication with the reservoir, occlusion ofthe cannula, whether the patch and injector are properly coupled, flowrate of the substance through the cannula, etc. A sensor of theplurality of input transducer/sensors may be selected from the groupconsisting of a conductivity sensor, impedance sensor, capacitancesensor, charge sensor, humidity and/or moisture sensor, temperaturesensor, heart rate sensor, interstitial pressure sensor, resistancesensor, distension sensor, acoustic sensor, vibration sensor, bloodpressure sensor, optical sensors (e.g., color sensor, light sensor,wavelength sensor), chemical sensor, movement and/or activity sensor,and a substance-tracking sensor. A sensor of the plurality of outputtransducers may be selected from the group consisting ofhaptic(vibration) transducers, audio transducers or visual transducers.These sensors may be used to detect, in non-limiting examples, theenvironmental conditions in which the subject is using the injector, thesubject's body temperature, heart rate, blood pressure, interstitialpressure, tissue density, skin distension, bleeding (e.g., internal orexternal), delivery of the medicament, dosage of the medicament todeliver and/or delivered to the subject, sweat quantity of the subject,and/or a plurality of analyte measurements from the subject (e.g., bloodglucose, blood oxygen, etc.). One or more measurements may be measuredor monitored prior to, contemporaneously, or following securing of thepatch. For example, the patch may be configured to measure one or morehealth or physiological parameters prior to injection to establish abaseline and/or calibration measurement of the one or more health orphysiological parameters. The patch may be secured to the body of thesubject separately from the injector. For example, the patch may besecured to the body of the subject and one or more measurements may becollected. Subsequent attachment of the injector (e.g., to the patchand/or the body of the user) may then allow for directing a substance tothe subject.

The transducer may comprise any useful components, e.g., a solenoid,motor, or micro-electro-mechanical systems (MEMS) actuator. In suchcases, the housing of the injector or patch may comprise electricallyconductive contacts providing both mechanical attachment and electricalcontact of the transducers or sensors, e.g., in an electronic sub-systemhoused in the injector.

The patch and/or injector may comprise a communication interface thatallows for transmitting and/or receiving data corresponding to theplurality of health or physiological parameters of the subject and/orparameters of the patch or injector. The data may be transmitted to anelectronic device in communication with the communication interface. Thecommunication interface may be a wireless communication interface, aWi-Fi interface, a near-field communication interface, or a Bluetoothinterface, as described herein. The electronic device may be a devicethat may communicate with the communication interface, e.g., a mobiledevice (e.g., smart phone, tablet, laptop, etc.). Alternatively, thecommunication interface may be a wired communication interface. In someexamples, the patch and/or injector may comprise a port forcommunication and/or power supply (e.g., universal serial bus (USB),USB-type C, etc.) for connection to the electronic device. The patchand/or injector may include an RFID tag that allows for information tobe transferred to and optionally, recorded by the injector and/or patchincluding but not limited to information about the drug. This may allowdata transmitted about the injection to include information about thedevice and the drug.

In some cases, the patch, injector, and/or electronic device maycomprise methods for data processing, data storage, and/or one or morefeedback loops. In one such example, the patch may monitor one or morephysiological parameters of the subject after injection to produce dataon the one or more physiological parameters of the subject. The data maybe transmitted through the communication interface to the electronicdevice (e.g., mobile device). In some cases, the mobile device maycomprise a method for processing the data and/or storing data (e.g., incomputer readable memory). Examples of processing include measurement ofa concentration of an analyte, identification of an analyte, comparingthe concentration of an analyte to a standard, calibration of themeasurement, summaries of information collected, statistics calculation,trend determination, etc. The processed data may subsequently be used toregulate, e.g., in a feedback loop, to regulate one or more parametersof the patch or injector. The processed data may also be sent directlyto a third party for further evaluation. For example, a measurement ofthe physiologic parameter may measure the concentration of an analyte ora substance (e.g., a drug or medicament). The data may be transmitted tothe electronic device, which may further process the data (e.g.,calibrate the concentration, compare to a standard, determination if adosage change is required etc.). Accordingly, the processed data may beused to change a device parameter, e.g., dosage of the substance to beadministered, flow rate of dispensing of the substance, etc. The data,processed data, or other signal may then be relayed back to the patch orinjector, such that the subsequent injection of the injector ismodulated (e.g., the next dosage is higher or lower). In anotherexample, a measurement of the physiologic parameter may measure patientbleeding (e.g., colorimetric, measurement of heme iron of blood, etc.).Detection of bleeding or substance leakage from the site may be used tomodulate (e.g., in a feedback loop) the subsequent administration rateor injection. In such examples, presence of patient bleeding may allowfor subsequent injections to be delayed, or to change a parameter of thecannula extension toward the body of the subject (e.g., force ofinjection, speed of injection, etc). In some cases, an electronic devicemay not be required, and the patch may be able to communicate with theinjector directly or through a communication interface. In such cases,the patch and/or injector may measure a device and/or physiologicalparameter of the subject and subsequently use the measurement toregulate a parameter of the injector or patch. In one non-limitingexample, the measurement of the parameter (e.g., blood glucose of thepatient) may regulate the dosage of a subsequent injection of theinjector.

In another example, the patch may monitor one or more parameters of thepatch and/or injector to produce data on the one or more parameters ofthe injector and/or patch. The data may be transmitted through thecommunication interface to the electronic device (e.g., mobile device).In some cases, the mobile device may comprise a method for processingthe data. Examples of processing include determination if device isproperly secured (e.g., if the adhesion force of the patch to the bodyof the subject is above or below a threshold value), whether the patchis properly connected to the injector, etc. The processed data maysubsequently be used to regulate, e.g., in a feedback loop, one or moreparameters of the patch or injector. For example, a measurement of theadhesion force of the patch to the body of the subject may be conducted.The data may be transmitted to the electronic device, which may furtherprocess the data (e.g., determine insufficient adhesion force).Accordingly, the processed data may be used to change a deviceparameter, e.g., activation a notification to the subject or other user,as described herein. The data, processed data, or other signal may thenbe relayed back to the patch or injector, such that a parameter of thepatch or injector is adjusted or requires adjustment before proceedingto inject again (e.g., administer another dosage of the substance). Insome cases, an electronic device may not be required, and the patch maybe able to communicate with the injector directly or through acommunication interface. In such cases, the patch and/or injector maymeasure a parameter of the patch and/or injector and subsequently usethe measurement to regulate that parameter or a different parameter ofthe injector or patch. In one non-limiting example, the measurement ofan insufficient adhesion force of the patch may, in a feedback loop,prevent subsequent injection of the injector until the patch is measuredas sufficiently adhered to the body of the subject.

The patch and/or injector may also be in communication or be capable ofcommunication with the subject or other user. In some cases, thecommunication with the subject or other user may comprise a feedbacksystem or loop. Alternatively, or in conjunction, the patch or injectormay be capable of notifying the subject or other user (e.g., physician,nurse, medical practitioner, clinician, etc.) on a device parameter,health or physiological parameter, or both. For example, the patch orinjector may be capable of producing sounds (e.g., to give directions tothe subject or other user), producing motion (e.g., vibration), or maycomprise visual indicators such as a light (e.g., light-emitting diode),a screen or display (e.g., a liquid-crystal display (LCD), organiclight-emitting diode, quantum dot display, or variations or derivativesthereof), or other visual indicator. Alternatively, or in conjunction,the patch or injector may comprise a user interface module. In suchexamples, the subject or other user may be able to interact with thepatch and/or injector. In one of such examples, the patch or injectormay comprise a screen or display that may produce a string of charactersor sounds that may be used to prompt the subject or other user torespond to a command. In another example, the patch or injector maycomprise a screen or display that may produce a string of characters orsounds that may be used to display an output or result, such as theresults of the measurement of a physiological parameter. The subject orother user may then be able to input a response or a command, e.g.,through a microphone, which may be in the housing of the patch and/orinjector, or through a button on the housing of the patch or theinjector with which the subject can interact. In some cases, thesubject's input into the patch or injector may result in modulation of aparameter of the patch or injector. In some cases, the subject or otheruser may be able to input a parameter, e.g., pain, discomfort, etc.,that may not be easily measurable or accessible from the patch orinjector. These parameters may then be communicated, e.g., through acommunication interface, to an external device (e.g., mobile device). Insome cases, the patch and/or injector may comprise feedback systems suchthat the input from the subject or other user may modulate a parameterof the patch or injector. For example, input of a pain parameter mayresult in modulation of the flow rate of the substance through thecannula or the frequency of administered doses of the substance.

The patch and/or injector may also be configured to communicate with aremote system. In some examples, the patch and/or injector may measureone or more physiological parameters of the subject or one or moreparameters of the patch and/or injector to produce data on the one ormore physiological parameters of the subject or the one or moreparameters of the patch and/or injector. The data may be transmitted toa remote server, a distributed computing network (e.g., for cloudcomputing). Processing of the data may then occur separately from thepatch and/or injector. In some cases, the processed data may then betransmitted to an electronic device (e.g., mobile device). In othercases, the processed data may then be transmitted to the patch and/orinjector, for modulation of a parameter of the patch and/or injector.Transmission of data to a remote server and/or to an electronic devicemay allow for the subject to monitor the one or more physiologicalparameters, and/or may additionally or alternatively allow forphysicians or caretakers to also monitor the one or more physiologicalparameters of the subject.

In another aspect, provided herein is a method for measuring a pluralityof health or physiological parameters from a subject. The method maycomprise (a) providing: (i) a patch comprising a first housing having aplurality of sensors and comprising an opening, and (ii) an injectorhaving a second housing comprising a cannula in fluid communication witha fluid flow path. The second housing may be coupled to the firsthousing of the patch, and the injector may comprise a reservoircomprising a substance and a fluid flow path in fluid communication withthe reservoir. The method may further comprise (b) securing the patch toa body of the subject; (c) when the patch is secured to the body of thesubject, directing the cannula through the opening to (i) direct thesubstance from the reservoir to the fluid flow path, and (ii) direct thesubstance from the fluid flow path into the subject through the cannula;and (d) using the plurality of sensors to (i) measure the plurality ofhealth or physiological parameters from the subject, and (ii) provideone or more outputs corresponding to the plurality of health orphysiological parameters from the subject.

Using embodiments of the disclosure, a person with any number ofphysical and/or mental conditions treatable with drugs administered withan injector, such as the devices described above, can be monitored toensure that the combination therapy (medicament and injector) is safeand efficacious. Data collected during monitoring of the patient andinjector attributes can be used by patients, caregivers, providers,payers, drug and device manufacturers to provide feedback to any of theaforementioned parties including confirmation of claims/outcomes andallowing for manual and/or automatic intervention by the patient and/ordevice to improve the safety and effectiveness of the therapy.

In one embodiment, illustrated in FIGS. 59 and 60, an injector of thetype described above is indicated in general at 402. The device includesa housing including a circular base 404. A ring-shaped skin attachmentlayer 406 is secured to the base of the injector with an adhesive andfeatures a pull tab 408. The underside of the attachment layer (visiblein FIGS. 59 and 60) is provided with an adhesive that provides a lowerholding force than the adhesive securing the attachment layer 406 to theinjector. As a result, the injector 404 may be removed from the body(e.g., skin) of a subject by pulling up on tab 408 away from the skin ofa subject.

In addition to the skin attachment layer 406, a patch, indicated ingeneral at 412 in FIG. 59, and as in an exploded view of FIG. 60, isattached to the bottom of the injector by a magnetic fasteningarrangement as will be explained in greater detail below. As analternative to the magnetic attachment, the patch could be attached tothe injector with adhesive or by other mechanical means.

While the patch and the skin attachment layer are illustrated as havingcircular profiles, alternative shapes may be used.

A generally conical skin boundary displacement extension 414 extendsfrom the bottom of the patch 412 and, as described previously,compresses the skin to help reduce tissue deflection or “tenting” uponcannula insertion. The extension 414 features a central orifice 416 thataligns with the dispense port of the injector.

In an alternative embodiment, as described in embodiments presentedabove, the skin boundary displacement extension may be part of, andextend from, the base 404 of the injector itself. In such an embodiment,a central hole may be provided in the center of the patch, with the holebeing smaller than the diameter of the base of the extension. When theinjector is positioned with the skin attachment layer securing thedevice against the skin, the extension expands the hole in the patch,and provides a path for the injector cannula or cannula to enter theskin when the device is activated or “fired” in the manner describedabove. The cannula may not pass directly through the material andprovide for the opportunity to clog the cannula or inject foreignbandage material into the skin from the cannula, see FIG. 16B. Theexpanded central hole of the patch closes to its original smaller sizewhen the injector is removed from the skin. An absorbent material may beoptionally deposited around the central hole of the patch to soak up anyblood or leakage. In this way, the patch acts as a ‘band aid’ after theinjection.

As in FIGS. 59 and 60, the skin attachment layer 406 features a centralopening 418 that is sized to receive the patch 412. While the embodimentof FIGS. 59 and 60 illustrates the patch 412 as being separate from theskin attachment layer 406, in alternative embodiments, the patch may becircumferentially joined to the skin attachment layer by a perforationarrangement. As yet another alternative, the patch 412 may be fastenedto the skin attachment layer via tabs circumferentially spaced about thepatch.

As illustrated in FIG. 60, the patch 412 includes a sensor 422, aprinted circuit board (PCB) chip 424 and a sensor adhesive layer 426.The PCB chip 424 and the sensor adhesive layer 426 are secured to thesensor 422 by adhesive or other fastening mechanisms. The sensoradhesive layer 426 includes a central window 428 through which, afterassembly, the extension 414 protrudes, as illustrated in FIG. 59. Thedownward facing surface 430 of the sensor adhesive layer 426 is providedwith an adhesive for securing the patch to the skin of a user.

The injector 402 and the patch 412 are configured so that the patch isapplied to the body (e.g., skin, digits) of a subject (e.g., user) asthe injector is attached. Furthermore, the patch 212 remains after theinjector 402 is removed. More specifically, as illustrated in FIG. 60, anumber of permanent magnets 432 are positioned and secured within thehousing of the injector 402. As examples only, the magnets may besecured within corresponding recesses 434 formed within the injectorhousing by adhesive, interference fit or other attachment arrangements,as described elsewhere herein. The top side of the sensor 422 features ametallic disk portion 436 (FIGS. 59 and 60) so that the patch is securedto the bottom of the injector via magnetic attraction. The adhesive onsurface 430 of the sensor adhesive layer 426 provides a holding forcewith the user's skin that is greater than the magnetic force holding thepatch to the injector. As an alternative to disk portion 436 beingmetallic, the disk portion may be provided with metallic portions,illustrated in phantom at 437 of FIG. 59, that correspond to and attractthe magnets of the injector. In an alternative embodiment, the metallicportion(s) of the patch may be provided with other shapes. A singlering-shaped metallic portion could also be used.

The use of magnets to secure the patch to the injector offers theadvantage of no exposed residual adhesive on the patch as it remains onthe patient. In addition, the magnets may be located precisely on theinjector, and corresponding metallic portions located on the patch, sothat we'll be able to control the amount and where the force is that is‘pulling’ on the patch when the injector is removed. As an alternativeto metallic portions on the injector, magnets may be used. In analternative embodiment, the magnets may be located on the patch and thecorresponding metallic portions may be located on the injector.

In an alternative embodiment, the patch 412 may be secured to the bottomof the injector by an adhesive (such as on the top side of sensor 422)that has less holding force than the skin-engaging adhesive on surface430 of the sensor adhesive layer 426.

In another alternative embodiment, the patch 412 may be secured to thebottom of the injector using mechanical features built into either thepatch, the injector or both with less holding force than theskin-engaging adhesive on surface 430 of the sensor adhesive layer 426.In such an embodiment, the skin attachment layer 406 of FIGS. 59 and 60may be eliminated so that the injector is held to the patient only viathe connection between the injector housing and the patch. In such anembodiment, both the injector and the patch are secured to the patientsolely by the sensor adhesive layer. Additional connections between thehousing of the injector and the sensor adhesive layer 426 could alsoexist (in addition to the connection of the injector to the sensoradhesive layer through the patch, as described elsewhere herein).

As illustrated in FIGS. 61 and 62, the PCB chip 424 features circuitryincluding a Bluetooth module with microcontroller/microprocessor 444that is connected to a battery 442 and antenna 448. In addition, theBluetooth module 444 is attached to sensor 422. The battery 442 providesfor the stored energy to power the system. The Bluetooth module 444 hasan integrated microcontroller/microprocessor. An example of a suitableBluetooth module is Dialog Semiconductor Part number DA14580-01UNA. Inalternative embodiments, the Bluetooth module may be separate from themicrocontroller/microprocessor. In some embodiments, directcommunication to the cloud may be used, such as, e.g., via cellular orother communication technologies.

As illustrated in FIG. 63, the injector 402 is provided with one or moresensors 450 a and 450 b that communicate with the Bluetooth module 444via Bluetooth. The sensors 450 a and 450 b may include transmitters andmay receive power from a battery also positioned within the injectorhousing. Alternatively, each sensor may have its own battery. Sensors450 a and 450 b may also be passive sensors that do not require batterypower. The sensors 450 a and 450 b may be chosen to provide a variety ofalternative functions as explained in greater detail below.

In alternative embodiments, communication between the sensors 450 a and450 b of the injector and the module 444 of the PCB chip 424 of thepatch may be accomplished by alternative wireless communicationarrangements know in the art. In further alternative embodiments, thesensors 450 a and 450 b may communicate with the module 444 of the PCBchip 424 via wire connection(s) that automatically disconnect when theinjector is removed from the patch and patient.

Of course the number of sensors 436, 450 a and 450 b may be varied fromwhat is illustrated in FIGS. 61-63.

The Bluetooth module 444 also enables the patch to transmit datacollected from sensors 422, 450 a and 450 b to a remote receiver such asa personal data device (such as a smart phone), a computer system ornetwork or the cloud. The remote receiver may collect the received datawithin, and build, a database.

In use, initially the injector features the patch attached (via themagnetic arrangement described above), as illustrated in FIG. 59. Aprotective backing sheet is removed from the skin attachment layer 406so that the adhesive on the surface facing away from the injector isexposed. This backing sheet also removably covers the adhesive onsurface 430 of the patch. The exposed adhesive surfaces of the injectorskin attachment layer 406 and the sensor adhesive layer 426 are thenpressed against the skin of a user so that the injector and the patchare attached thereto.

In the illustrated embodiment, the patch 412 has multiple functions.First it senses and transmits the state of the injector to a remotereceiver (such as a personal data device, for example, a smart phone, acomputer network or the cloud), i.e. has the injector been activated sothat the injection is being given or has the injection been completed.The second thing is the patch transmits the state of the patient viadata collected from the sensors to the remote receiver. This can be donebefore, during or after the injection and before, during or afterattachment and or removal of the injector. For example, the temperatureof the skin at the injection site and the skin ‘color’ may be detectedvia a simple temperature monitor combined with an LED/phototransistorcircuit included in the sensor 422 for transmitting the tissuetemperature and color during and after the injection. This feature canbe useful during a clinical study, to alert the staff if there is aninjection site reaction (ISR), and it could quantify the ISR based ontemperature and tissue color. The third thing is the patch couldinteract directly injector based on data received from the injectorand/or data received from the patient and/or data received from itself.The patch could interact with the injector as a control mechanismincluding adjustment of the flowrate (faster, slower or pause), vibratefor user notification and/or pain management, provide an audible soundto provide direction or notification to the user, visual indicators toindicate change, alerts, notifications or information to the user, ormechanical interactions to cause a change in state of the injectorincluding but not limited to retraction of the button to stop thedelivery in the instance of data from the patient (for example, pain) ordata from the device (for example, premature removal or fall-off).

A heartrate sensor could also be included in sensors 422 to obtain apatient EKG signal if useful and/or a strain gage sensor may be providedto detect the skin pressure exerted by the extension 414 FIGS. 59 and60. Patient mobility, position and location data may be collected bycorresponding sensors (such as an accelerometer, GPS sensor or the like)incorporated in sensor 422. In addition, a couple of electrodes(included in sensor 422) in contact with the skin could detect skinimpedance and detect leakage or detachment. Furthermore, the skincontact electrodes could detect a premature removal of the device, i.e.removal of the device before the device has completed its cycle.

Upon completion of an injection by the injector, the injector can beremoved from the patient's skin by pulling tab 408 (FIGS. 59 and 60)away from the patient's skin. As this is done, the patch is decoupledfrom the injector allowing only the patch to be adhered to the patient.The detachable nature of the monitoring patch provides a physician orthe like with the ability to monitor the patient continuously betweeninjections.

Alternatively, the patch could be initially decoupled from the injectorand placed on the patient to monitor before start ofadministration/injection of a drug or drugs. This could provide baselinedata about the patient prior to the administration/injection.

Alternatively, the patch could be applied independently of the injectorand placed on the patient to monitor baseline conditions (e.g., abaseline physiologic parameter) before the start of theadministration/injection of drug or drugs. The injector could then becoupled to the patch prior to start of the injection.

FIGS. 64-65 illustrate exploded views of another embodiment of the patchand injector. The patch 6401 includes an adhesive layer 6403 and asensor 6405, which may comprise the PCB chip. In this embodiment, and infurther embodiments described below, the patch and/or injector may eachinclude one or more sensors, as described in the previous embodiments.The sensor 6405 may adhere to the adhesive layer 6403, which may be usedto secure the patch 6401 to the body of the subject. The injector 6407and the patch 6401 can be configured so that the patch is applied to thebody of the subject as the injector 6407 is attached. Alternatively, orin addition to, the injector 6407 and the patch 6401 may be coupledprior to securing the patch 6401 and injector 6407 to the body of thesubject.

The patch 6401 may be coupled to the injector 6407 using an interlockingbayonet mechanism. For instance, the injector 6407 can compriseprotruding elements 6409, which can interface with detents 6411 in thepatch 6401. The detents 6411 may prevent free rotation of the patch 6401and the protruding elements 6409 in a first configuration. Upon twistingof the patch 6401 or the injector 6407, the injector 6407 may be movedto a second configuration, in which the protrusions 6409 no longercouple to the detents 6411, and thus the injector 6407 can be de-coupledor removed from the patch 6401 (e.g., after the patch is secured to thebody of the subject and the medicament has been delivered).

FIG. 66 illustrates an exploded view of another embodiment of the patchand injector. The patch 6601 includes an adhesive layer 6603 and asensor 6605, which may comprise the PCB chip. The sensor 6605 may adhereto the adhesive layer 6603, which may be used to secure the patch 6601to the body of the subject. The injector 6607 and the patch 6601 can beconfigured so that the patch is applied to the body of the subject asthe injector 6607 is attached. Alternatively, or in addition to, theinjector 6607 and the patch 6601 may be coupled prior to securing thepatch 6601 and injector 6607 to the body of the subject.

The patch 6601 may be coupled to the injector 6607 by coupling or matingparts 6609 and 6611. Part 6609 may be coupled to the injector 6607(e.g., in a recess 6613) whereas part 6611 may be coupled to the patch6601. Parts 6609 and 6611 may be magnets and may be secured to therecess 6613 of the injector 6607 and the patch 6601, respectively, viaadhesive, interference fit, or other attachment arrangements. Theadhesive layer 6603 can provide a holding force with the subject's body(e.g., skin) that is greater than the magnetic force holding the patchto the injector.

FIG. 67 illustrates another embodiment of the patch and injector. Thepatch 6701 includes an adhesive layer 6703 and a sensor 6705, which maycomprise the PCB chip. The sensor 6705 may adhere to the adhesive layer6703, which may be used to secure the patch 6701 to the body of thesubject. The injector 6707 and the patch 6701 can be configured so thatthe patch is applied to the body of the subject as the injector 6707 isattached. Alternatively, or in addition to, the injector 6707 and thepatch 6701 may be coupled prior to securing the patch 6701 and injector6707 to the body of the subject.

The patch 6701 may be coupled to the injector 6707. For instance, thesensor 6705 may be configured to couple to the injector 6707 by fittinginto a recess 6713. The injector can comprise a safety tab or strip. Theadhesive layer 6703 can provide a holding force with the subject's body(e.g., skin) that is greater than the magnetic force holding the patchto the injector.

FIG. 68 shows a cross-sectional view of the coupled injector and patchof FIG. 67. The injector can comprise a latch 6717 connected to a spring(e.g., torsion spring) 6715. In Panel A, the patch and injector may bein a first configuration (“Ready position”), where the device is locked,and the patch remains attached to the injector. The button 6719, whichcan be used to direct the cannula toward the subject when depressed, isin a start or ready position and ready for actuation. In panel B, theinjector may be transformed (e.g., via rotation, removal of the safetytab 6801, or both), into a second configuration (“Lock-out position”).In the second configuration, the torsion spring may be released, therebytranslating the latch 6717 to a different position. In such aconfiguration, the injector is removable from the patch, and the button6719 may be in the raised position illustrated in panel B, preventingdepression of the cannula out of the injector.

FIG. 69 illustrates another embodiment of the patch and injector. Thepatch 6901 includes an adhesive layer 6903, a sensor 6905, which maycomprise the PCB chip, and an attachment module 6911. The attachmentmodule 6911 may comprise an adhesive or other fastening mechanism toadhere the patch 6901 to the injector 6907. The sensor 6905 may adhereto the adhesive layer 6903, which may be used to secure the patch 6901to the body of the subject. The injector 6907 and the patch 6901 can beconfigured so that the patch is applied to the body of the subject asthe injector 6907 is attached. Alternatively, or in addition to, theinjector 6907 and the patch 6901 may be coupled prior to securing thepatch 6901 and injector 6907 to the body of the subject. The patch 6901may additionally comprise an external layer comprising perforations6921. For instance, the external layer may comprise a plastic, polymer(e.g., thermosensitive polymer, e.g., shrink wrap), or other material.The external layer can be configured to be removed prior to use of thepatch and injector. When the device is ready for use, the external layermay be removed by pulling on a pull tab 6923, which may remove theexternal layer via the perforations 6921, thereby allowing removal ofthe external layer.

FIG. 70 shows a cross-sectional view of the coupled injector and patchof FIG. 69. A dimension of the patch (e.g., the width or diameter) maybe substantially similar as the diameter of the injector.

FIG. 71 illustrates another embodiment of the patch and injector. Thepatch 7101 includes an adhesive layer 7103 and a sensor 7105, which maycomprise the PCB chip. The sensor 7105 may adhere to the adhesive layer7103, which may be used to secure the patch 7101 to the body of thesubject. The injector 7107 and the patch 7101 can be configured so thatthe patch is applied to the body of the subject as the injector 7107 isattached. Alternatively, or in addition to, the injector 7107 and thepatch 7101 may be coupled prior to securing the patch 7101 and injector7107 to the body of the subject. The patch 7101 may be coupled to theinjector 7107 via latch 7113. The latch 7113 may be coupled to theinjector 7101 using a press-fit mechanism, and subsequent pushing orapplying force to the latch 7113 can result in detachment of the patch7101 from the injector 7107. Alternatively or in addition to, the latch7113 may comprise a hook that can adhere to the housing of the injector7107. The latch may then be actuated by pressing or applying a force onthe latch 7113 and pulling the latch away from the housing of theinjector 7107, which allows for detachment of the patch 7101 from theinjector 7107.

FIG. 72 shows a cross-sectional view of the coupled injector and patchof FIG. 71. The latch 7113 comprises a hook to adhere to the housing ofthe injector. By applying a force 7115 on the latch, the hook can bereleased, thereby allowing decoupling or detachment of the patch fromthe injector.

FIG. 73 illustrates another embodiment of the patch and injector. Thepatch 7301 includes an adhesive layer 7303 and a sensor 7305, which maycomprise the PCB chip. The sensor 7305 may adhere to the adhesive layer7303, which may be used to secure the patch 7301 to the body of thesubject. The injector 7307 and the patch 7301 can be configured so thatthe patch is applied to the body of the subject as the injector 7307 isattached. Alternatively, or in addition to, the injector 7307 and thepatch 7301 may be coupled prior to securing the patch 7301 and injector7307 to the body of the subject. The patch 7301 may be coupled to theinjector 7307 via flanges 7311 and ring 7313. The ring 7313 may comprisea rubber or other elastomeric material. The ring 7313 can couple to theinjector 7307 by fitting into the grooves of the flanges 7311 and 7321.The flanges 7311 may be complementary to the flanges 7321 of the patch7301.

FIG. 74 shows a cross-sectional view of the coupled injector and patchof FIG. 73. The flanges 7321 of the patch may fit complementarily to theflanges 7311 of the injector. By applying a force 7415 on the flanges7321, the patch may be detached from the injector.

FIG. 75 illustrates another embodiment of the patch and injector. Asshown in Panel A, the patch 7501 includes an adhesive layer 7503 and asensor 7505, which may comprise the PCB chip. The sensor 7505 may adhereto the adhesive layer 7503, which may be used to secure the patch 7501to the body of the subject. The injector 7507 and the patch 7501 can beconfigured so that the patch is applied to the body of the subject asthe injector 7507 is attached. Alternatively, or in addition to, theinjector 7507 and the patch 7501 may be coupled prior to securing thepatch 7501 and injector 7507 to the body of the subject, as shown inpanel B. The housing of the patch 7501 and sensor 7505 may partiallysurround the housing of the injector 7507. The patch may also comprisewinged features 7513. The features 7513 may allow for better grip of thesubject, or for positioning the device.

FIG. 76 illustrates another embodiment of the patch and injector. Inpanel A, the patch 7601 includes an adhesive layer 7603 and a sensor7605, which may comprise the PCB chip. The sensor 7605 may adhere to theadhesive layer 7603, which may be used to secure the patch 7601 to thebody of the subject. The injector 7607 and the patch 7601 can beconfigured so that the patch is applied to the body of the subject asthe injector 7607 is attached. Alternatively, or in addition to, theinjector 7607 and the patch 7601 may be coupled prior to securing thepatch 7601 and injector 7607 to the body of the subject, as shown inpanel B. The patch 7601 may be coupled to the injector 7601 via a latch7613, which may secure to a protrusion 7611 of the injector 7611. Thelatch may be rotatable, such that in certain configurations, the latch7613 does not rest on the protrusion 7611, allowing decoupling of thepatch 7601 from the injector 7607.

FIG. 77 illustrates another embodiment of the patch and injector. Inpanel A, the patch 7701 includes an adhesive layer 7703 and a sensor7705, which may comprise the PCB chip. The sensor 7705 may adhere to theadhesive layer 7703, which may be used to secure the patch 7701 to thebody of the subject. The injector 7707 and the patch 7701 can beconfigured so that the patch is applied to the body of the subject asthe injector 7707 is attached. Alternatively, or in addition to, theinjector 7707 and the patch 7701 may be coupled prior to securing thepatch 7701 and injector 7707 to the body of the subject, as shown inpanel B. The patch 7701 may be coupled to the injector 7707 via anadhesive (e.g., at the interface between the patch 7701 and injector7707). The patch may also comprise, e.g., on the adhesive layer 7703, aprotruding feature 7713. The protruding feature may allow for decouplingof the patch 7701 from the injector 7707 when a subject presses or pullson the feature 7713.

FIG. 78 shows a cross-sectional view of the coupled injector and patchof FIG. 77. The protruding feature 7713 may be used to pry the patchfrom the injector.

FIG. 79 illustrates another embodiment of the patch and injector. InPanel A, the patch 7901 includes an adhesive layer 7903 and a sensor7905, which may comprise the PCB chip. The sensor 7905 may adhere to theadhesive layer 7903, which may be used to secure the patch 7901 to thebody of the subject. The injector 7907 and the patch 7901 can beconfigured so that the patch is applied to the body of the subject asthe injector 7907 is attached. Alternatively, or in addition to, theinjector 7907 and the patch 7901 may be coupled prior to securing thepatch 7901 and injector 7907 to the body of the subject, as shown inpanel B. The patch 7901 may be coupled to the injector 7907 via flanges7913 on the patch and complementary protrusions 7911 on the injector7907. The flange 7913 may latch or hook onto the protrusions 7911. Theflange 7913 can be locked in a first configuration and in a secondconfiguration, the flange 7913 may be released, such as to allowdecoupling of the patch 7901 from the injector 7907.

FIG. 80 illustrates another embodiment of the patch and injector. Thepatch 8001 includes an adhesive layer 8003 and a sensor 8005, which maycomprise the PCB chip. The sensor 8005 may adhere to the adhesive layer8003, which may be used to secure the patch 8001 to the body of thesubject. The injector 8007 and the patch 8001 can be configured so thatthe patch is applied to the body of the subject as the injector 8007 isattached. Alternatively, or in addition to, the injector 8007 and thepatch 8001 may be coupled prior to securing the patch 8001 and injector8007 to the body of the subject. The patch 8001 may be coupled to theinjector 8007 via thread features 8013 on the patch 8001 andcomplementary threads (not shown) on the injector 8007. The threadfeatures 8013 may screw onto the complementary threads of the injector8007. Coupling and decoupling of the patch 8001 to the injector 8007 canoccur by twisting the patch 8001 or injector 8007.

FIG. 81 shows a cross-sectional view of the coupled injector and patchof FIG. 80. The threads 8013 of the patch may be complementary tothreads of the injector. Upon twisting of the injector counterclockwise,the patch may be released from the injector.

FIG. 82 illustrates another embodiment of the patch and injector. Thepatch 8201 includes an adhesive layer 8203, a sensor 8205, which maycomprise the PCB chip, and a deformable surface 8213. The sensor 8205may adhere to the adhesive layer 8203, which may be used to secure thepatch 8201 to the body of the subject. The injector 8207 and the patch8201 can be configured so that the patch is applied to the body of thesubject as the injector 8207 is attached. Alternatively, or in additionto, the injector 8207 and the patch 8201 may be coupled prior tosecuring the patch 8201 and injector 8207 to the body of the subject.The patch 8201 may be coupled to the injector 8207 via the deformablesurface 8213. In a first configuration, the deformable surface 8213 maycomprise gradated holes 8215 that can be used to secured screws or pins8217 of the injector 8207 to the patch 8201. Upon pressing of the twoends of the deformable surface 8213 toward one another, the deformablesurface may assume a second configuration, in which the gradated holes8215 are large enough such that the screws or pins 8217 may detach fromthe deformable substrate 8213 of the patch 8201, thereby decoupling thepatch 8201 from the injector 8207.

FIG. 83 shows a cross-sectional view of the coupled injector and patchof FIG. 82. In this configuration, the deformable substrate 8213 islocked onto the injector. By pressing the ends of the deformablesubstrate 8213 together, the gradated holes are moved such that the pins8217 of the injector may be lifted from the deformable substrate andpatch, thereby decoupling the patch from the injector.

FIG. 84 illustrates another embodiment of the patch and injector. Thepatch 8401 includes an adhesive layer 8403 and a sensor 8405, which maycomprise the PCB chip. The sensor 8405 may adhere to the adhesive layer8403, which may be used to secure the patch 8401 to the body of thesubject. The injector 8407 and the patch 8401 can be configured so thatthe patch is applied to the body of the subject as the injector 8407 isattached. Alternatively, or in addition to, the injector 8407 and thepatch 8401 may be coupled prior to securing the patch 8401 and injector8407 to the body of the subject. The patch 8401 may be coupled to theinjector 8407 via ridges 8413 on patch 8401, which may be used to securethe patch 8401 to the injector 8407 via a snap or press fit. Theinjector 8407 may additionally comprise complementary features that cansecure to the ridges 8413. Decoupling of the patch 8401 to the injector8407 can occur by twisting the patch 8401 or injector 8407 or by pullingapart the patch 8401 from the injector 8407.

FIG. 85 shows a cross-sectional view of the coupled injector and patchof FIG. 84. The ridges 8413 of the patch may be configured to couple tocomplementary features 8513 (e.g., bumps, ridges, cavities) of theinjector. Decoupling of the patch and injector may occur by applyingsufficient force to pry apart the ridges 8413 and complementary features8513.

FIG. 86 illustrates another embodiment of the patch and injector. Thepatch 8601 includes an adhesive layer 8603 and a sensor 8605, which maycomprise the PCB chip. The sensor 8605 may adhere to the adhesive layer8603, which may be used to secure the patch 8601 to the body of thesubject. The injector 8607 and the patch 8601 can be configured so thatthe patch is applied to the body of the subject as the injector 8607 isattached. Alternatively, or in addition to, the injector 8607 and thepatch 8601 may be coupled prior to securing the patch 8601 and injector8607 to the body of the subject. The patch 8601 may be coupled to theinjector 8607 by coupling or mating parts 8609 and 8611. Part 8609 maybe coupled to the injector 8607 (e.g., in a recess 8613) whereas part8611 may be coupled to the patch 8601. Parts 8609 and 8611 may comprisemagnets and may be secured to the recess 8613 of the injector 8607 andthe patch 8601 via adhesive, interference fit, or other attachmentarrangements.

FIG. 87 shows a cross-sectional view of the coupled injector and patchof FIG. 86. The magnets 8611 of the patch may be configured to couple tomagnets 8609 of the injector. Decoupling of the patch and injector mayoccur by applying sufficient separate the magnets of the patch from themagnets of the injector.

In some instances, it may be useful to have both the patch and theinjector secured to the body of the subject. In such cases, the injectormay additionally comprise features that may be configured to couple thehousing of the injector to the body of the subject. For example, theinjector may comprise an adhesive layer. The adhesive layer of theinjector may be separate from the mechanism used to secure the patch tothe body of the subject.

FIG. 88 illustrates another embodiment of the patch and injector, whereboth the patch and injector are configured to couple to the body of thesubject. In Panel A the patch 8801 includes an adhesive layer 8803 and asensor 8805, which may comprise the PCB chip. The sensor 8805 may adhereto the adhesive layer 8803, which may be used to secure the patch 8801to the body of the subject. The patch 8801 can be configured so that thepatch 8801 is applied to the body of the subject, which may be securedseparately from the injector 8807, which can also comprise an adhesivelayer 8813. Alternatively, or in addition to, the injector 8807 and thepatch 8801 may be coupled prior to securing the patch 8801 and injector8807 to the body of the subject, as shown in Panel B. The patch 8801 maybe coupled to the injector 8807 by coupling or mating parts, asdescribed elsewhere herein. The adhesive layer 8803 of the patch 8801may comprise a feature 8811, which may allow for separation of theadhesive layer 8803 of the patch 8801 from the adhesive layer 8813 ofthe injector 8807. In such an example, the patch 8801 may be secured tothe body of the subject and may not be removable from the subject untilthe injector 8807 has been removed. In some instances, the attachment oradhesive force of the patch adhesive layer 8803 to the body (e.g., skin)of the subject may be greater than the attachment or adhesive force ofthe injector 8807 to the body (e.g., skin) of the subject. In someinstances, the attachment or adhesive force of the patch adhesive layer8803 to the body of the subject may be greater than the attachment oradhesive force of the patch 8801 coupled to the injector 8807.

FIG. 89 shows a cross-sectional view of the coupled injector and patchof FIG. 88. Both the patch and the injector may comprise an adhesivelayer. The adhesive layer 8813 of the injector may be configured tosecure the injector to the body of the subject.

In some cases, the patch or an opening of the patch may comprise apierce-able membrane. The pierceable membrane may comprise an opening(e.g., slit, hole) through which the cannula of the injector may passwhen the cannula is directed from the injector to the body of thesubject. In some instances, the pierce-able membrane may adhere orotherwise be secured to the body of the subject. In such cases, thepierce-able membrane may comprise an absorbent material, e.g., to absorbbodily fluids (e.g., blood, sweat, etc.) from the subject. It will beappreciated that any of the above-described embodiments may comprise apatch comprising sensors (e.g., on the PCB chip), and alternatively orin addition to, the patch may comprise the pierce-able membrane, whichmay comprise an absorbent material.

FIG. 90 shows an example patch, or portion thereof, comprising apierceable membrane coupled to an adhesive layer of an injector. InPanel A the patch 9001 includes an adhesive layer 9003. The patch mayalso comprise a sensor (not shown) that may adhere to the adhesive layer9003. The adhesive layer 9003 may be used to secure the patch 9001 tothe body of the subject. The patch 9001 can be configured so that thepatch 9001 is applied to the body of the subject, which may be securedseparately from the injector 9007, which can also comprise an adhesivelayer 9013. Alternatively, or in addition to, the injector (not shown)and the patch 9001 may be coupled prior to securing the patch 9001 andinjector to the body of the subject, as shown in Panel B. The patch mayalso comprise an opening 9021, which may comprise a pierceable membrane9023. In some cases, the opening 9021 is a slit, and the material of thepierceable membrane 9023 comprises a self-healing elastomer (i.e., theopening closes after the cannula is retracted away from the body of thesubject). The adhesive layer 9003 of the patch 9001 may comprise afeature 9011 (e.g., tab), which may allow for separation of the adhesivelayer 9003 of the patch 9001 from the adhesive layer 9013 of theinjector 9007. FIG. 91 shows a bottom-up and cross-sectional view of thepatch of FIG. 90. The patch comprises an opening 9021, which is anopening of a pierceable membrane 9023. In some cases, the opening 9021is a slit, and the material of the pierceable membrane 9023 comprises aself-healing elastomer and/or absorbent material. The adhesive layer9003 of the patch may comprise a feature 9011 (e.g., tab), which mayallow for separation of the adhesive layer 9003 of the patch from theadhesive layer of the injector.

FIG. 92 shows an exploded view of the adhesive layers of the patch andinjector of FIG. 90. The patch 9001 comprises a pierceable membrane9023, which can comprise an opening 9021. The pierceable membrane 9023can be decoupled from the patch and may remain secured to the body ofthe subject (e.g., as a bandage). In some cases, the opening 9021 is aslit, and the material of the pierceable membrane 9023 comprises aself-healing elastomer as well as absorbent materials. The adhesivelayer 9003 of the patch 9001 may comprise a feature 9011 (e.g., tab),which may allow for separation of the adhesive layer 9003 of the patchfrom the adhesive layer 9013 of the injector.

In some examples, the patch may be configured to couple to anautoinjector. FIG. 93 shows an example patch comprising a pierceablemembrane coupled to an autoinjector 9307. In Panel A the patch 9301includes an adhesive layer 9303. The patch may also comprise a sensor(not shown) that may adhere to the adhesive layer 9303. The adhesivelayer 9303 may be used to secure the patch 9301 to the body of thesubject, and in some cases, the adhesive layer 9303 may be secured tothe body of the subject. In such cases, the adhesive layer 9303comprises an absorbent material (e.g., bandage pad) and will remain onthe body of the subject following injection. The patch 9301 can beconfigured so that the patch 9301 is applied to the body of the subject,which may be secured separately from the autoinjector 9307.Alternatively, or in addition to, the autoinjector 9307 and the patch9301 may be coupled prior to securing the patch 9301 to the body of thesubject, as shown in Panel B. The patch may also comprise an opening9321, which may be a part of a pierceable membrane 9323. In some cases,the opening 9321 is a slit, and the material of the pierceable membrane9323 comprises a self-healing elastomer (i.e., the opening closes afterthe cannula is retracted away from the body of the subject). Theadhesive layer 9303 of the patch 9301 may comprise a feature 9311 (e.g.,tab), which may allow for separation of the adhesive layer 9303 of thepatch 9301 from the autoinjector. In some instances, the patch 9301 mayalso comprise a sensor unit 9305, which may comprise a PCB chip.

Embodiments of the disclosure provide a combination of reporting boththe injector and the patient state during and after the injection. Thepatch and associated battery and circuitry are initially physicallycoupled to the injector. In an alternative embodiment, the patch couldbe applied and allow for connection of the one or more injectors. Thepatch circuit can communicate, e.g., via a communication interface, tothe receiver the one or more parameters of the injector before beingsecured to the patient. Once the patch/injector is secured to thepatient, the patch communicates both the patient and injector states.When the injector is removed, the patch remains on the patient directlyon the injection site to transmit the state of the injection site. Thepatch could remain there for just a few hours if that is enough time toinsure no reaction has occurred, or the patch can remain until the nextinjector/patch is applied. That is, upon completion of an injection, apatient may remove the injector and keep the patch on. The patch maycontinue to provide data (up to several days) until the nextadministration where it is replaced.

There are a number of situations where the physician might be reluctantto let the patient self-administer at home because of potential adversereactions. If the patch were able to monitor for any potentialcomplications (ISR's, heart rate, respiration, temperature, etc), andtransmit a signal to the physician if there was anything unusual, itmight give the physician confidence to send the patient home forinjections. In an outcome-based healthcare model, there is a significantbenefit to the system knowing that the patient is improving with thetherapy with quantitative data as evidence. In the instance where thepatient's health is acutely changing (or over the long-term), theability for a treating physician to get involved earlier throughnotification based on trends of continuously accumulated data andintervene has long term benefit to the patient and overall outcome.

This type of “detachable” monitoring patch can also be extremely usefulin clinical studies. The patients could be monitored for a variety ofparameters during the study that could increase compliance and reducecomplications and could even make enrollment easier. For example, if apatient is required to remain in the physician's office for 4 hoursafter each injection to monitor for ISR's, they might be able toeliminate this wait with the patch monitoring, which could result inimproved recruitment. Moreover, such a device can allow for longitudinalstudies that measure patient compliance and that provide for increasedaccuracy of data transmission (e.g., by obviating the need for manualrecording of data).

The patch concept is not limited to the injector described above. Thispatch with and/or without electronics can also be adapted to otherinjectors. These devices could include autoinjectors. In view of theabove, embodiments of the disclosure may provide, for example, a patchthat can include electronics or just comprise a bandage material (seee.g., FIGS. 90-93). In some examples, the patch may be connected to theinjector, and securing of the patch and injector may occur via a forceapplied to the patch and injector, thereby obviating the need for aseparate patch application. Alternatively, the patch may be applied bythe injector directly to the injection site and may covers the cannulaentry point with an expandable/contractible element. As describedelsewhere herein, the patch may be magnetically coupled to the injector.In some examples, the patch may be mechanically coupled to the injectorwith a user-intended release mechanism. In some cases, the patch may besmaller than the total adhesive patch used to adhere the injector. Thepatch may comprise an adhesive pad that is the same size or smaller thana dimension of the patch. In some examples, the patch may transmitinjector data prior to application to the patient, transmit bothinjector and patient data after application to the patient, and/ortransmit patient data after removal of the injector.

Example Applications/Uses

As illustrated in FIG. 94, the sensor 9401 of the patch may customizedper patient or physician requirements to measure specific device and/orpatient attributes or physiological parameters.

One or more sensors may be used to measure the device and/or patientattributes or physiological parameters. Non-limiting examples of typesof sensors include temperature sensors, interstitial pressure sensors,skin resistance sensors, skin distention sensors, acoustic sensors,vibration sensors, heart rate sensors, blood pressure sensors (BP inFIG. 94), color or other optical sensors, moisture sensors, chemicalsensors (e.g., that sense, measure or detect drug concentration,Histamine, oxygen, etc.).

One or more sensors may be used to measure one or more deviceattributes, such as the presence of skin, tracking of the delivery ofthe substance, and/or occlusion of the device (e.g., the cannula of theinjector).

As illustrated in FIG. 95, the sensors may alternatively be incorporatedinto the sensor adhesive layer 9501. As noted previously, any usefulcombination of patient sensing attributes may provide for meaningfulevidence of conclusions or outcomes. For example: a site reaction may bedetected using a temperature measurement, a skin resistance and/orimpedance measurement, and a color measurement, or any combinationthereof. In another example of correlating pain with measured sitereaction, a temperature measurement, a skin resistance or impedancemeasurement, a color measurement, skin distention measurement, orinterstitial pressure measurement, or any combination thereof, may beused. In yet another example of monitoring contraindicated activitiesduring the therapy, a vibration measurement, a heart rate measurement,and/or a moisture measurement (e.g., to indicate sweat levels), orcombinations thereof, may be used. In another example, monitoring forwet injection may use a moisture measurement. Another example of subjectoutcomes may include monitoring for poor bio-absorption by measuringinterstitial pressure, tissue density, temperature, skinresistance/impedance, color, and/or skin distention. In another exampleof monitoring for systemic adverse reaction, a moisture (sweat)measurement, EMG/ECG, vibration (e.g., a proxy for restlessness),increased sound (e.g., as a proxy for stomach or intestine gas levels)may be used, or any combination thereof.

FIG. 96 shows another embodiment of the sensor unit. The sensor unit maycomprise, for instance, a PCB 9601, a Hall effect sensor 9602, a coincell battery 9603, a buzzer 9604, a haptic vibration sensor 9605, a skinpresence sensor 9606, a humidity and temperature sensor 9607, a 3Daccelerometer and gyroscope 9608, a Reed switch 9609 and a low-powercore processor 9610. The sensor may comprise more than one layer, withdifferent sensors, batteries, and other components distributed in eachlayer or in distinct layers.

The patch may be used post-injection, after injector removal, for avariety of functions. In non-limiting examples, the patch may be used toclose up the injection site to prevent bleeding, use moisture detectionto detect any injection site leakage/bleeding, monitor skin temperatureand color and pressure to detect ISR's, monitor heartrate/EKG, monitorpatient position—upright or recumbent, and/or monitor skinchemistry/sweat.

In some embodiments, the patch can communicate with the patient toremind him or her of the next injection time, provide an alarm if thereis injection site reaction or leakage, increase in temperature, color,heartrate etc. Communications between the patch and patient could bevisual, audible or tactile.

Embodiments of the patch may be used during an injection to monitor thestate of the injector/injector to determine if, for example, theinjector is filled, the volume or quantity of the substance (e.g., drugor medicament) that has been filled into the injector, the injector isremoved from storage or transfer device base, if the injector is placedon skin, if the safety strip is removed, if the button is pressed, thatinjection begins, the gas gauge position including delivery tracking,button depressed for pause, the button retracts cannula, injectioncomplete, if the injector is removed from skin, or any of thepost-injector parameters associated with measurement of patientphysiological parameters previously discussed.

Additional Features/Embodiments

In alternative embodiments, a sensor may detect if another patch istransmitting, or the existing patch was removed. The patch could beclear to allow the patient to see the injection site, and it would be asunobtrusive as possible so the patient could wear the patch and continueto conduct daily activities (shower, swim, etc.).

In further alternative embodiments, sensing elements may be providedthat can measure device attributes including: presence of skin (cannularetraction or fall-off sensing), delivery indicator tracking (includingfill and dispense), occlusion detection, drug temperature, device status(On/Off Transfer Base, On/Off Patient, Button Status, Pause Events,etc), flowrate, internal injector pressure/injection pressure, adhesiveadhesion.

Further embodiments may incorporate patient and device sensing elementsto allow for manual and/or automatic intervention (management) on theinjector. For example, the flow rate of the injector may be adjusted(e.g., faster, slower, stopped/paused) based on site reaction sensinginformation (automatic), pain information from patient (manual),bio-absorption rate (automatic) or any combination or variationsthereof.

Further embodiments may vibrate (for pain management or notification touser)—Vibration element in injector and/or patch, based on site reactionsensing information, pain information from Patient (manual) or painsensing information, interstitial pressure/site distention information(automatic), or any combination or variations thereof.

In further embodiments, sound may be provided (e.g., for notificationand/or information transfer to the user)—Sound element in injectorand/or patch and activated based on sensing information from thepatient, device sensing elements (occlusion, drug temp, deliveryindication, etc.), or combinations or variations thereof.

In further embodiments, visual indicators may be provided (e.g.,indication change, for notification and/or information transfer to theuser)—LED or equivalent on injector and/or patch and activated based onsensing information from patient, device sensing elements, the positionof the retract button—e.g., to detect premature removal/falloff, sensinginformation from injector (skin sensing, etc.), sensing information fromthe patient (high pressure, temp, etc.), or combinations or variationsthereof.

In further embodiments, a lockout for the injector button depression(e.g., for security or preventing drug mis-use) may be provided andactivated based on sensing information from injector (drug temperature,etc.), sensing information from patient (skin sensing, etc.), sensinginformation from the mobile application (e.g., time since lastinjection, user authentication), or variations or combinations thereof.

In further embodiments, subcutaneous/transcutaneous electrical neuralstimulation (TENS) (e.g., for pain management or bio-absorption) may beprovided. In such cases, an electrode element in cannula and/or patchmay be activated based on site reaction sensing information, paininformation from patient (manual) or pain sensing information,interstitial pressure/site distention information (automatic), orvariations or combinations thereof.

Further embodiments may predict remaining injection time based on e.g.,sensing flow rate and fill volume, sensing device pressure and backpressure, drug temperature, body temperature, and fill volume.

Potential features of still further embodiments may also include: thepatch sensing if another patch has been applied, the patch being clearto allow visualization of the tissue below, the patch communicatingdirectly with the user/patient, audible signals (e.g., “hey—time foryour next injection” or “Call the doctor—you have an ISR”), and/or othertactile options, vibration, electrical stimulation, visual options,light emitting diodes, of the patch regularly transmitting data toreceiver or directly to the cloud or intermittent data broadcasting.

Mobile Applications

In another aspect, disclosed herein are systems and methods forgenerating mobile applications for monitoring one or more health orphysiological parameters. A mobile application may be generated using avariety of methods, e.g., an application programming interface (API).The mobile application may comprise a plurality of useful features andmay be configured to interact with other mobile applications. In somecases, the mobile application may be configured to display themeasurements of one or more physiological parameters from the subject ora parameter of the patch and/or injector. The mobile application maycomprise feedback systems that allow for subject or other user input,which may allow for modulation of the patch and/or injector (e.g.,amount of substance dispensed). The mobile application may alsocommunicate, e.g., through the communication interface, with a remoteserver. In some cases, the remote server may be a part of or communicatewith a separate electronic device (e.g., mobile device, laptop), whichmay allow for a clinician or physician to monitor the physiologicalparameters of the subject. In some cases, the mobile application mayallow for inputs from the subject of non-measurable parameters (e.g.,pain, discomfort, etc.). The mobile application may also comprisesoftware for data processing. Data processing may include, innon-limiting examples, statistical analysis of data, trend plotting andanalysis, and graphical representation of the data. In some cases, themobile application may be capable of interfacing or combining with othermobile applications, such as a lifestyle tracking application (e.g., tomonitor diet and activity), or other useful mobile applications, e.g.,location tracking, accelerometer, calendars (e.g., to send reminders),etc.

FIG. 97 illustrates schematically an example workflow of a mobileapplication for monitoring one or more health or physiologicalparameters. A mobile device 9700 may be a laptop, a tablet, a phone, orother electronic device (e.g., portable electronic device). Upon openingor selection of the application on the mobile device 9700, a loadingscreen 9710 may be presented, followed by a menu screen 9720. The menuscreen 9720 may provide a plurality of functions 9730. Non-limitingexamples of functions 9730 may include starting a new infusion, infusionhistory, training videos, additional information, and patient profile.Upon selection of a function 9730 (e.g., infusion history), a secondscreen 9740 pertaining to the function may be presented. In such anexample, the subject may be presented with a calendar. In process 9750,the subject may select a second function on the second screen 9740 whichpresents a third screen 9760. The third screen may display one or morehealth or physiological parameters of the subject, the device, or thedelivery of the substance to the subject (e.g., prescription, time, dayof week, regiment, reminders to the patient, alarms, vibrations, etc.).In an example third screen 9980, the calendar may comprise selectabledates that provide information on the one or more health orphysiological parameters of the subject on each selected date. In anexample fourth screen 9990, the calendar of the mobile application maydisplay additional information, e.g., when the subject has missed aninfusion. In an example fifth screen 9790, the calendar of the mobileapplication may display additional information, e.g., when the subjecthas received an infusion.

FIG. 98 illustrates schematically an example workflow of a mobileapplication for monitoring one or more health or physiologicalparameters, which may be used in conjunction with one or more workflowsof the mobile application. Upon selection of a function 9730 (e.g.,starting a new infusion, see FIG. 97) from the menu screen 9720 (seeFIG. 97), screen 9810 may appear. The mobile application may allow fordetection of the substance or medicament, e.g., scanning of a barcode orquick response code (QR code). The mobile application may be integratedwith another application on the mobile device such as a camera anddisplay the camera on screen 9820. Screen 9830 shows an example screenof a scanned QR code, which may present information on the substance ordevice. The mobile application may subsequently verify the drug anddevice compatibility and/or other parameters of the drug/device, e.g.,expiration date, dosage, etc. In cases where the drug or device isinappropriate for the subject (e.g., expired drug), screens 9842 or 9844may appear, which notify the subject of the inappropriateness of thedrug or device. In cases where the drug or device is appropriate for thesubject, screen 9850 may appear, which may provide guidance,instructions, or directions to the subject. Instructions may bepresented in a continuous scroll format, as exemplified in screen 9852.The mobile application may then be paired with the device. On examplescreen 9860, additional guidelines may be provided to the subject.Safety features may be included in the application, e.g., if a safetymeasure (e.g., safety tab) has not been performed by the subject, themobile application may notify the subject. Screen 9870 may display oneor more device parameters (e.g., infusion status, injection of thecannula into the body of the subject, etc.). Incomplete infusion maypresent screen 9872 which may indicate the status of the infusion andmay include other indications of the device parameters (e.g., “devicepaused”). Upon completion of the delivery of the substance or drug,screen 9880 may be displayed, which may indicate the status of theinfusion. In some cases 9880 may present the subject with options torank the infusion experience. Multiple steps in the process may alsocomprise communication steps 9854 (e.g., via Bluetooth, Wi-Fi) to aseparate device, cloud computing, clinician server, etc.

FIG. 99 illustrates another example workflow of a mobile application formonitoring one or more health or physiological parameters, which may beused in conjunction with one or more workflows of the mobileapplication. Upon selection of a function 9730 (e.g., training videos,see FIG. 97) from the menu screen 9720 (see FIG. 97), screen 9900 mayappear. The mobile application may comprise a variety of tutorials ortraining information for the subject. FIG. 99A demonstratesschematically a plurality of devices or systems which may be integratedwith the mobile application. Upon selection of a device or system (e.g.,syringe transfer system, handheld system, vial transfer system,reconstitution system), screens 9905, 9910, 9915, or 9920 may appear,which may comprise a video demonstrating a tutorial or method of use ofthe device or system. FIG. 99B illustrates schematically another exampleworkflow of a mobile application for monitoring one or more health orphysiological parameters, which may be used in conjunction with one ormore workflows of the mobile application. Upon selection of a function9730 (e.g., additional information, see FIG. 97) from the menu screen9720 (see FIG. 97), screen 9925 may appear, which may comprise a menudisplaying one or more health of physiological parameters or one or moredevice parameters. Additional information may be available to thesubject (e.g., prescription information, device information, etc.). Uponselection of a function in the menu, screen 9930 or 9945 may appear,which may further comprise options to display additional information,e.g., safety information (e.g., screen 9935 or 9950) or questions andanswers (e.g., screen 9940 or 9955). FIG. 99C illustrates schematicallyanother example workflow of a mobile application for monitoring one ormore health or physiological parameters, which may be used inconjunction with one or more workflows of the mobile application. Uponselection of a function 9730 (e.g., patient profile, see FIG. 97) fromthe menu screen 9720 (see FIG. 97), screen 9970 may appear, which maycomprise a menu. The menu may include options for the subject to viewand/or input patient information (e.g., gender, height, weight, activitylevel). Additional settings may be implemented in the mobileapplication, such as alarms, alerts, emails, notifications, etc.

Computer Systems

The present disclosure provides computer systems that are programmed toimplement methods of the disclosure. FIG. 100 shows a computer system10001 that is programmed or otherwise configured to transmit and/orreceive data, and process data. The computer system 10001 can regulatevarious aspects of the present disclosure, such as, for example, methodsfor data analysis, subject monitoring and measurement of physiologicalor health parameters, and providing an output of the physiological orhealth parameters. The computer system 10001 can be an electronic deviceof a user or a computer system that is remotely located with respect tothe electronic device. The electronic device can be a mobile electronicdevice.

The computer system 10001 includes a central processing unit (CPU, also“processor” and “computer processor” herein) 10005, which can be asingle core or multi core processor, or a plurality of processors forparallel processing. The computer system 10001 also includes memory ormemory location 10010 (e.g., random-access memory, read-only memory,flash memory), electronic storage unit 10015 (e.g., hard disk),communication interface 10020 (e.g., network adapter) for communicatingwith one or more other systems, and peripheral devices 10025, such ascache, other memory, data storage and/or electronic display adapters.The memory 10010, storage unit 10015, interface 10020 and peripheraldevices 10025 are in communication with the CPU 10005 through acommunication bus (solid lines), such as a motherboard. The storage unit10015 can be a data storage unit (or data repository) for storing data.The computer system 10001 can be operatively coupled to a computernetwork (“network”) 10030 with the aid of the communication interface10020. The network 10030 can be the Internet, an internet and/orextranet, or an intranet and/or extranet that is in communication withthe Internet. The network 10030 in some cases is a telecommunicationand/or data network. The network 10030 can include one or more computerservers, which can enable distributed computing, such as cloudcomputing. The network 10030, in some cases with the aid of the computersystem 10001, can implement a peer-to-peer network, which may enabledevices coupled to the computer system 10001 to behave as a client or aserver.

The CPU 10005 can execute a sequence of machine-readable instructions,which can be embodied in a program or software. The instructions may bestored in a memory location, such as the memory 10010. The instructionscan be directed to the CPU 10005, which can subsequently program orotherwise configure the CPU 10005 to implement methods of the presentdisclosure. Examples of operations performed by the CPU 10005 caninclude fetch, decode, execute, and writeback.

The CPU 10005 can be part of a circuit, such as an integrated circuit.One or more other components of the system 10001 can be included in thecircuit. In some cases, the circuit is an application specificintegrated circuit (ASIC).

The storage unit 10015 can store files, such as drivers, libraries andsaved programs. The storage unit 10015 can store user data, e.g., userpreferences and user programs. The computer system 10001 in some casescan include one or more additional data storage units that are externalto the computer system 10001, such as located on a remote server that isin communication with the computer system 10001 through an intranet orthe Internet.

The computer system 10001 can communicate with one or more remotecomputer systems through the network 10030. For instance, the computersystem 10001 can communicate with a remote computer system of a user(e.g., Located at a physician's office or a physician's mobile device).Examples of remote computer systems include personal computers (e.g.,portable PC), slate or tablet PC's (e.g., Apple® iPad, Samsung® GalaxyTab), telephones, Smart phones (e.g., Apple® iPhone, Android-enableddevice, Blackberry®), or personal digital assistants. The user canaccess the computer system 10001 via the network 10030.

Methods as described herein can be implemented by way of machine (e.g.,computer processor) executable code stored on an electronic storagelocation of the computer system 10001, such as, for example, on thememory 10010 or electronic storage unit 10015. The machine executable ormachine-readable code can be provided in the form of software. Duringuse, the code can be executed by the processor 10005. In some cases, thecode can be retrieved from the storage unit 10015 and stored on thememory 10010 for ready access by the processor 10005. In somesituations, the electronic storage unit 10015 can be precluded, andmachine-executable instructions are stored on memory 10010.

The code can be pre-compiled and configured for use with a machinehaving a processer adapted to execute the code or can be compiled duringruntime. The code can be supplied in a programming language that can beselected to enable the code to execute in a pre-compiled or as-compiledfashion.

Aspects of the systems and methods provided herein, such as the computersystem 10001, can be embodied in programming. Various aspects of thetechnology may be thought of as “products” or “articles of manufacture”typically in the form of machine (or processor) executable code and/orassociated data that is carried on or embodied in a type of machinereadable medium. Machine-executable code can be stored on an electronicstorage unit, such as memory (e.g., read-only memory, random-accessmemory, flash memory) or a hard disk. “Storage” type media can includeany or all of the tangible memory of the computers, processors or thelike, or associated modules thereof, such as various semiconductormemories, tape drives, disk drives and the like, which may providenon-transitory storage at any time for the software programming. All orportions of the software may at times be communicated through theInternet or various other telecommunication networks. Suchcommunications, for example, may enable loading of the software from onecomputer or processor into another, for example, from a managementserver or host computer into the computer platform of an applicationserver. Thus, another type of media that may bear the software elementsincludes optical, electrical and electromagnetic waves, such as usedacross physical interfaces between local devices, through wired andoptical landline networks and over various air-links. The physicalelements that carry such waves, such as wired or wireless links, opticallinks or the like, also may be considered as media bearing the software.As used herein, unless restricted to non-transitory, tangible “storage”media, terms such as computer or machine “readable medium” refer to anymedium that participates in providing instructions to a processor forexecution.

Hence, a machine readable medium, such as computer-executable code, maytake many forms, including but not limited to, a tangible storagemedium, a carrier wave medium or physical transmission medium.Non-volatile storage media include, for example, optical or magneticdisks, such as any of the storage devices in any computer(s) or thelike, such as may be used to implement the databases, etc. shown in thedrawings. Volatile storage media include dynamic memory, such as mainmemory of such a computer platform. Tangible transmission media includecoaxial cables; copper wire and fiber optics, including the wires thatcomprise a bus within a computer system. Carrier-wave transmission mediamay take the form of electric or electromagnetic signals, or acoustic orlight waves such as those generated during radio frequency (RF) andinfrared (IR) data communications. Common forms of computer-readablemedia therefore include for example: a floppy disk, a flexible disk,hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD orDVD-ROM, any other optical medium, punch cards paper tape, any otherphysical storage medium with patterns of holes, a RAM, a ROM, a PROM andEPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wavetransporting data or instructions, cables or links transporting such acarrier wave, or any other medium from which a computer may readprogramming code and/or data. Many of these forms of computer readablemedia may be involved in carrying one or more sequences of one or moreinstructions to a processor for execution.

The computer system 10001 can include or be in communication with anelectronic display 10035 that comprises a user interface (UI) 10040.Examples of UI's include, without limitation, a graphical user interface(GUI) and web-based user interface.

Methods and systems of the present disclosure can be implemented by wayof one or more algorithms. An algorithm can be implemented by way ofsoftware upon execution by the central processing unit 10005. Thealgorithm can, for example, process data, perform statistical analyses,plot or graphically represent data, and provide feedback for one or moresystems disclosed herein (e.g., the patch and/or injector).

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. It is not intendedthat the invention be limited by the specific examples provided withinthe specification. While the invention has been described with referenceto the aforementioned specification, the descriptions and illustrationsof the embodiments herein are not meant to be construed in a limitingsense. Numerous variations, changes, and substitutions will now occur tothose skilled in the art without departing from the invention.Furthermore, it shall be understood that all aspects of the inventionare not limited to the specific depictions, configurations or relativeproportions set forth herein which depend upon a variety of conditionsand variables. It should be understood that various alternatives to theembodiments of the invention described herein may be employed inpracticing the invention. It is therefore contemplated that theinvention shall also cover any such alternatives, modifications,variations or equivalents. It is intended that the following claimsdefine the scope of the invention and that methods and structures withinthe scope of these claims and their equivalents be covered thereby.

What is claimed is:
 1. A method for detecting an injection site reactionin a subject, comprising: (a) providing a patch comprising a sensor,wherein said patch is secured to a body of said subject; and (b) withsaid patch secured to said body of said subject, using said sensor tomeasure one or more health or physiological parameters from saidsubject, wherein said one or more health or physiological parameters areindicative of a presence or a likelihood of an injection site reactionon said body of said subject.
 2. The method of claim 1, furthercomprising notifying said subject of said presence or said likelihood ofsaid injection site reaction.
 3. The method of claim 1, wherein saidpatch is coupled to an injector.
 4. The method of claim 3, wherein saidinjector is removably coupled to said patch.
 5. The method of claim 3,wherein said injector is an autoinjector.
 6. The method of claim 3,wherein said injector comprises a reservoir comprising a substance,wherein said reservoir is in fluid communication with a cannula fordelivering said substance to said body of said subject.
 7. The method ofclaim 6, further comprising, subsequent to (a), directing said substancethrough said cannula into said body of said subject.
 8. The method ofclaim 7, wherein (b) occurs subsequently to said directing.
 9. Themethod of claim 3, wherein said injector receives data from said patch.10. The method of claim 9, wherein said injector receives said data fromsaid patch subsequent to (b).
 11. The method of claim 9, wherein saiddata is indicative of said presence or said likelihood of said injectionsite reaction.
 12. The method of claim 1, wherein said sensor measuressaid one or more health or physiological parameters on a surface of saidbody of said subject.
 13. The method of claim 12, wherein said sensormeasures said one or more health or physiological parameters from a skinof said body of said subject.
 14. The method of claim 1, wherein saidsensor is not inserted into said body of said subject.
 15. The method ofclaim 1, wherein (b) comprises measuring a temperature, tissue color,pressure, moisture level, heart rate, an upright or recumbent positionof said subject, skin chemistry, sweat quantity, sweat composition,impedance, or blood oxygen of said subject.
 16. The method of claim 1,wherein said patch further comprises one or more transducers configuredto generate an output signal, wherein said output signal is a vibrationsignal, audio signal, electrical signal, or visual signal, or acombination thereof.
 17. The method of claim 16, wherein said outputsignal is indicative of said presence or said likelihood of saidinjection site reaction.
 18. The method of claim 1, wherein said patchcomprises a communication interface for transmitting data correspondingto said one or more health or physiological parameters to an electronicdevice in communication with said communication interface.
 19. Themethod of claim 18, wherein said communication interface comprises awireless communication interface.
 20. The method of claim 18, whereinsaid electronic device is a mobile device.
 21. The method of claim 20,further comprising, subsequent to (b), transmitting said data to saidmobile device via said communication interface.
 22. The method of claim21, wherein said mobile device processes said data.
 23. The method ofclaim 22, wherein said mobile devices processes said data to determinesaid presence or said likelihood of said injection site reaction. 24.The method of claim 20, wherein said mobile device further comprises amobile application.
 25. The method of claim 24, wherein said mobileapplication further collects one or more parameters as input from saidsubject.
 26. The method of claim 25, wherein said one or more parameterscorrespond to pain or discomfort of said subject associated with saidinjection site reaction.
 27. The method of claim 25, further comprisingusing at least (i) said one or more parameters as input from saidsubject and (ii) said one or more health or physiological parameters todetermine a presence or a likelihood of an injection site reaction onsaid body of said subject.
 28. The method of claim 24, wherein,subsequent to (b), said presence or said likelihood of said injectionsite reaction is displayed on said mobile application.
 29. The method ofclaim 1, wherein said patch further comprises an additional sensor.